The microenvironment recruits Tregs to tumor tissue by chemotaxis
Hypoxia induces differentiation of T-cells to Tregs
Low pH induces differentiation of T cell into Tregs
Different gene expression profiles in metabolic pathways of E
Downstream effects of mTORC1, which include modulation of cell growth, proliferation, metabolism and ion-channel expression, are primarily mediated by ribosomal biogenesis (proteins S6K and S6) and protein translation (4E-BP1 and eIF4E)
Reactions are numbered according to the key
In the case of the canonical TGF–β signaling pathway, this results in the activation of SMAD family transcription factors SMAD–2 and –3 which, upon phosphorylation, form complexes with SMAD–4 and translocate to the nucleus, where they act in transcriptional complexes as regulators of pro–fibrotic down–stream genes []
(A) Potential mechanisms involved in propagation of α-syn. Spreading mec... (B) Molecules and signaling pathways involved in α-syn-mediated microgli...
A scheme to explain how CP-AMPARs may trigger LTP2
Role of macrophages in hepatitis C virus infection-associated inflammation
The effects of mild and aggressive mechanical stimulations on LRP6, JNK signaling, eNOS production, and calcium ions in cardiomyocytes
Neurotrophic factor (NTFs) signaling pathways
Schematic representation of the mammalian canonical Hh signaling pathway
Schematic of metabolic pathways involved in glucose, fructose, and xylose catabolism in B
KEGG pathway analysis of differentially regulated genes in Jurkat cells after treatment with N4-Eru, depicting the affected genes in Notch signaling pathway
Significant deregulated key signaling nodes of JAK-STAT signaling pathway are represented in Jurkat cells after treatment with N4-Eru
Significant deregulated key signaling nodes of JAK-Wnt signaling axis are represented in Jurkat cells after treatment with N4-Eru
Nuclear factor-Œ∫B (NF-Œ∫B) signaling pathway
CRISPR/Cas9-based approaches for modeling kidney disease
Immune-related features and pathways predictive of response to immune checkpoint blockade
Tumor necrosis factor-Œ± pathway for necroptosis
a Extrusion of Ca+2 from the cytosol is accomplished by Ca+2 uptake into the ER via SERCA and Ca+2 accumulation in mitochondria
Role of triggering receptor expressed on myeloid cells-2 (TREM2) in microglial survival and metabolism
Regulative mechanisms of brain SIRT1 in metabolic homeostasis
SIRT1 protects against cerebral ischemic injury in multiple mechanisms
Netrin-1 signaling pathways (adapted from )
Activation of the Hippo pathway involves SAV, mammalian STE20‐like protein kinase 1 (MST1), MST2, MOB, and large tumour suppressor 1 and 2 (LATS1/2) and results in the phosphorylation and inactivation of the transcriptional co‐activator YAP impeding cardiomyocyte proliferation
Binding of insulin molecule to insulin receptor leads to auto-phosphorylation of tyrosine residues present on insulin receptor
A standard place is illustrated as a circle representing proteins involved in the pathway
. A proposed diagram for the casticin-mediated inhibitory effects on the migration and invasion of breast cancer cells.
The regulatory effects on immune-related pathways induced by a group of compounds from health-strengthening herbs
Glutamine inter-tissue metabolic flux starting in skeletal muscle, liver, and gut continues in the immune cells
KDM5A function and its expression control in proliferating NPC and differentiating astrocyte
Contributions of activated/recruited stromal cells in endometrial cancer (EC) progression
Systemic effects of increased adiposity on EC progression
Main components of the Hippo pathway and the current Hippo-targeted inhibitors discussed in this review
Core analyses network predictions for HBoV-infected CuFi-8 cells
Role of the innate and adaptive immune cells following the irradiation of tumour cells
Diagramatic representation of the proposed signaling mechanisms mediating FGF2 versus S117A-FGF2 protection from Dox-induced damage
Figure illustrates differently the results obtained for Q6 using Explore Relationships tool
Effect of SPPL2a deficiency on IFN-γ machinery
The Toll or TLR signaling pathway activates Hippo signaling in innate immune cells
Model of the feedback regulation of AMPK by protein acetylation
Three apoptotic pathways (Extrinsic, intrinsic and granzyme pathways)
Schematic depiction of the anti-apoptotic role of the Arg/N-end rule pathway via targeted degradation of several pro-apoptotic protein fragments during induction of apoptosis in the context of apoptotic cell death signaling
The schematic diagram of c-mesenchymal–epithelial transition (c-MET) activation signaling pathways
Targeting HGF/c-MET pathway in digestive system cancers by microRNAs
Basic TGFβ signaling diagram along with a program of TGFβ-regulated genes that contribute to the EMT
Schematic diagram showing the effects of Kir4.1 inhibition on neuronal excitability and astrocytic BDNF expression
A schema illustrating the regulation of the autophagic pathway under diverse stressful conditions in cancer cells
Schematic representation of the biological activities of KM and its effects on the AGE-induced mitochondrial/cytochrome c-mediated apoptosis pathway in GMCs
Cartoon showing the major signaling pathways targeted by phytochemicals in cancer
The role of AMPK in class IIa histone deacetylases traffic in rat soleus muscle at the initial stages of gravitational unloading (modified from [])
IL-24 activates PKA to induce apoptosis in breast cancer cells
The response to immunotherapy in pancreatic ductal adenocarcinoma (PDAC) relies on destroying cancer cells as well as on breaking the stromal barrier and flaring up immune function
Schematic diagram of TGF-β signaling in palatal fusion
Signalling by pregnancy hormones prolactin (PrL) and placental lactogen (PL) through the prolactin receptor (PrlR) through the Jak/Stat pathway improves glucose stimulated insulin secretion (GSIS), prevents apoptosis and promotes proliferation and expansion
Mechanisms of p12I in the endoplasmic reticulum (ER) of infected cells
Correlation networks of main potential biomarkers in response to T2DM rats
The proposed model has been divided into parts corresponding to the biological phenomena: (a) Janus kinases and signal transducer and activator of transcription (JAK-STAT) pathway stimulated by interferon gamma (IFN); (b) innate immune responses; (c) p50/p65 translocation to the nucleus in macrophages M1, smooth muscle cell (SMC) and endothelial cell (EC); (d) gram-negative bacterial infections; (e) activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B)—the canonical pathway via IB phosphorylation by kinase complex (IKK) (MyD88-dependent signaling pathway); (f) activation of caspase 1 (by tumor necrosis factor (TNF) and also by binding with STAT binding element (SBE) sequences of interferon regulatory factor I (IRF1); (g) IL-18 synthesis (caspase 1-dependent pathway); (h) IL-18-IL-18R complex formation; (i) negative regulation of IL-18 (by inhibition of caspase 1) caused by nitric oxide (NO); (j) NO synthesis; (k) cardiovascular disease influenced by NO-dependent pathway; (l) TNF receptor-associated factor 2 (TRAF2) and receptor-interacting serine/threonine-protein (kinase 1 (RIP1) ubiquitination; (m) macrophages polarization; (n) lipid peroxidation (oxLDL); (o) IL-18 synthesis (caspase 1-independent pathway) and neighboring endothelial cells stimulation; (p) regulation of TNFR1 signaling; (r) the role of IL-1, IL-23, IL-6, high level of IL-10 and IL-12 (released by classically activated macrophages M1); (s) atherosclerosis progression; (t) attracting of monocytes (classically activated macrophages M1); (u) formation of apoptosome and activation of effector caspases 3, 6, 7; (w) high level of active caspase 8; (x) inhibition of caspase 8 and inhibition of apoptosis (by a high level of cFLIPs); (y) STAT6 upregulation promotes M2 macrophage polarization to suppress atherosclerosis
Representative model of leptin-induced EMT signaling
Schematic representation summarizing the transforming growth factors-beta (TGF-β) receptor complexes and signaling pathway in endothelial cells
Schematic representation of RA’s signaling via the RAR-RXR pathway
Representative image of the participation of SARA in the TGF-β signaling pathway
The possible model of Leptin and Immune response in malnutrition coupled infectious diseases
Molecular pathways of the neuro-immune hemostasis model
Proposed pathway for the complete utilization of carbaryl as the carbon and nitrogen source in Pseudomonas sp
T helper cell differentiation signaling pathway
Signaling pathways in osteoclasts involving V-ATPases
Proposed model of glycogen synthesis regulation by insulin in endometrial epithelial cells to provide nutrition to an implanted embryo
Mechanisms linking U34-enzymes to melanoma cell survival and resistance to targeted therapy
A final figure summarizing the major findings of this study and showing the integration of the lncRNA–microRNA–mRNA network and epigenetic regulation pathways
Genetics and molecular pathways for PPGLs Pathways for the New Genes; Placing the New into Perspective
Iron metabolism in prostate cancer microenvironment
The main brain-immune system pathways and feedback loops illustrating the interconnected effects of physical and emotional stress in health
Proposed pathway of antitumor effects of SDA in PCa cells
Major signaling pathways and therapeutic targets in CLL cells
Model for Subolesin/Akirin function in immune response pathways
The mechanisms of DMTN in the invasion and metastasis of CRC
The effects of morphine on neuronal transmission in the descending pain pathway
Effects of repeated morphine treatment on glial and neuronal signaling in the PAG
Schematic summary of the possible mechanism for GLCCI1 in glucocorticoids pathway
A schematic representation of the main molecular pathways linked to inflammatory and immunomodulatory activities modulated by Curcumin and Echinacea
The high-energy donor UDP-GlcNAc is provided by the hexosamine biosynthetic pathway (HBP) and is connected to UDP-GalNAc and CMP-NeuAc
A proposed schematic diagram of the PNS protection on BBB endothelial cells
Postulated cellular mechanisms of 20-HETE bioactions in the blood vessel wall
The proposed signal pathway with THSG and ADM in MCF-7 cells.Abbreviations: ADM, Adriamycin; THSG, 2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside
Blue arrows indicate the regulation among genes in the PI3-kinase pathway (arrows with vertical short line segments represent inhibition role of up-stream genes)
MAPK affects the activity of transcription factors via phosphorylation
Model of resistance to MET and MET/MAPK/ERK inhibition in DFCI358
Possible mechanism for epigenetic silencing of Lgr5 and induction of senescence in intestinal epithelial organoids derived from aged mice
Main targets and related signaling pathways involved in the targeted therapy for R/M HNSCC
PD-L1/PD-1 signaling pathway and the correlated network
Schematic model of HPV-driven carcinogenesis
Schematic overview of miRNA targets in fish immune system
Network visualization of top primary hits
Processes of liver fibrosis progression and regression during human hepatosplenic schistosomiasis
Impact of i-proteasome subunits on innate immune signaling in myeloid cells
Cholesterol biosynthetic pathway and relative expression changes for genes encoding related enzymes
Effect of resveratrol on the proliferation, invasion, metastasis, and apoptosis of tumor cells
Antitumor effects of emodin and chrysophanic acid
The proposed crosstalk between surface TLRs and dysregulated metabolic factors in diabetes, by interfering with NF-Œ∫B signaling pathway, and induced proinflammatory nuclear gene overexpression; e.g.IL-1β, IL-18, and TNF-Œ±
Cytoplasmic chromatin DNA activates the cGAS‐STING pathway and induces type I IFN and senescence‐associated secretory phenotype (SASP) production, which promote cellular senescence
Integrated Analysis Reveals Genomic and Expression Alterations in Signaling Pathways in HNSCC Differing in HPV Status
Proinflammatory and anti-inflammatory effects of IFN-β in CF: (A) IFN-β triggers JAK/STATsignaling pathway activation (STAT1, STAT3, and STAT3 proteins)
Cross-talk among different signaling pathways involved in MDSCs expansion, activation and function
The red boxes framed the most annotated KOs components in the pathway
. The top-ranked enriched canonical pathway identified in malignant CMTs using IPA: Cyclins and cell cycle regulation pathway.
. Apoptosis signalling pathway: The second-ranked enriched canonical pathway identified in malignant CMTs.
. Dendritic cell maturation: Second enriched canonical pathway in benign CMTs, identified using IPA.
Schematic representation of the inhibitory effect of HLSC-EVs and of TKIs alone or in combination on PI3K pathway and Erk
Several Wnt pathways were enriched in lung tissue Tregs
. Involvement of PHIP in the IGF1R pathway.
DANCR interacts with RXRA, and highly promotes GSK3β phosphorylating RXRA, and inhibits RXRA binding with PIK3CA promoter to upregulate its transcription, resulting in activating PI3K/AKT signaling pathway and TNBC tumorigenesis
Validated target genes (grey nodes) mapped to pathway annotations derived from literature and gene ontology using Ingenuity Pathway Analysis (IPA, http://www.ingenuity.com) A  Mir143 regulatory network B and Mir145 regulatory network.
Schematic illustration representing metabolic and transport proteins hypothesized from the genome of Ca
Schematic figure for PTS-mediated signaling pathways
Increased P2X4R expression after nerve injury via the actions of fibronectin in activated microglia
lncRNAs regulate hepatic fibrosis via TGF-β signaling pathway
Retrograde neurotrophic signalling organelles and their main destinations after arrival to the cell body
Triacylglycerol (TAG) synthesis in Drosophila: biochemistry and main regulatory pathways
Triacylglycerol (TAG) lipolysis in Drosophila: biochemistry and main regulatory pathways
Schematic of the TLR pathway and let-7e target mRNAs
Mitochondrial homeostasis is ensured through the coordination of mitochondrial biogenesis, dynamics, and autophagy
The age-related surge in generation of reactive oxygen species (ROS) arising primarily from the accumulation of dysfunctional mitochondria causes nuclear DNA damage and activates 5′-AMP-activated protein kinase (AMPK) signalling
Cardiomyocyte energy status regulates autophagy via metabolic signalling
This schematic shows E4orf1 specifically activates the distal insulin signaling by increasing AKT phosphorylation, AS160 phosphorylation and Glut4 translocation for glucose uptake under conditions when proximal insulin signaling pathway is inhibited with insulin receptor (S961) and IGF-1 (PPP) agonist
Mechanism of post-operative neuroinflammation.DAMPs and PAMPs activate the downstream pathway involved in inducing the production of TNFŒ±, as well as other proinflammatory mediators via NF-Œ∫B
Schematic diagram of the regulatory effects of miR-1292 on hADSC senescence and osteoblastic differentiation
A schematic model illustrating that miR-10b mediated function in osteogenic and adipogenic differentiation of hADSCs
Known and novel BP associations in the TGFβ signalling pathway
In B cells, the balance of BCR activation initiation, amplitude and duration can be influenced by a specific immunoglobulin structure, adaptor molecules (e.g.
Zinc and zinc transporters are involved in FcŒµRŒô-mediated mast cell activation
Proposed role of βCaMKII in regulation of COX-2/PGE2 neuroinflammatory signaling pathway and depression-like behaviors
A schematic representation illustrating the signaling molecules that regulate the PD-1/PD-L1 transcription
KEGG analysis of hsa-miR-210 target genes
Possible mechanisms of synergistic actions of the LABA/LAMA combination against inflammation
The overview of complement cascade activation and targets of inhibitors
Putative inhibitory pathway of Ac-ME in mediating the inflammatory response
Diagram of the mitogen-activated protein kinase pathway
(A) Vasorin 3D structure: Cartoon representation of the structure model... (B) Vasorin major pathways: Vasn was first described as an inhibitor of...
Schematic diagram showing the possible pathways involved in the activation of astroglial Cx43 hemichannels and Panx1 channels evoked by in vivo ethanol exposure during adolescence
Key interconnected metabolic pathways and their relevance to mTORC1 activation
The effect of different preconditioning stimuli in the MSCs response
Summary of the potential mechanisms of vaccine NSEs
Epidermal growth factor receptor pathway in patients with wild-type and mutant BRAF and KRAS
Schematic model of the HCV life cycle and involved Rab proteins
Expression differences in males and females in response to reduced insulin signaling for immune response genes
Expression differences within the IIS/TOR pathway for the four comparison types
The protein–protein network and pathway analysis
MALAT1 in cancer pathways.Notes: MALAT1 promotes generation of the six phenotypes of cancer
Scheme summarizing the protective effects of UTI on LPS-induced RAW264.7 cells
Schematic diagram of the molecular actions of CTLA-4 and PD-1 on inhibiting T cell function
Representative terpenoid biosynthesis pathway with cognate heat maps for transcript levels of genes from S
MAP of “p53 Signaling” pathway in (A) HSAEC and (B) A549 cells treated with 1 μM PG over 24 h. Predictions were calculated based upon DEGs from the experimental dataset overlaid onto the Ingenuity Knowledge Base in IPA.
Polyamine biosynthetic pathway in single-celled parasitic eukaryotes
Role of the APC tumor suppressor gene in signaling expression of genes regulating the polyamine pathway
Moderate heat stress induces nerve growth factor (NGF) signaling including downstream activation of AKT and ERK as well as cyclic AMP responsive element-binding protein 1 (CREB1) transactivation
Regulatory model for the flow pathway of central carbon metabolism and a proposed scheme for lipid biosynthesis in T
The proposed mechanisms by which Adam8 deficiency in leukocytes and/or lung parenchymal cells leads to exaggerated cigarette smoke (CS)-induced chronic obstructive pulmonary disease in mice
Schematic illustration of a molecular mechanism for AA effect on learning strategy
Schematic representation of the involvement of several TMEMs in tumor growth through the TGF-β signaling pathway
Potential genetic determinants of cardiovascular risk in SLE
JAK2 overexpression alleviates C2C12 myoblasts I/R injury through the AKT and ERK1/2 pathway
Main lipid-lowering effects of berberine through the APMK pathway
B cell receptor (BCR) signaling pathways
A) Axl expression can be elevated by TGFβ and e... B) Axl can be upregulated in cancer cells after... C) Axl on tumor cells can regulate PD-L1 expres...
Bioinformatic analysis of differentially expressed proteins (DEPs) identified in this study
CBL0137 exhibits its antitumor activity via multiple pathways
DT-13 promoted mitochondrial apoptosis and inhibited metastasis via suppressing PI3K/Akt pathway
Top two networks (A and B) identified by Ingenuity Pathway Analysis as overrepresented within the list of 245 genes (P < 0.005) dysregulated in human IAPP transgenic (HIP) vs. wild-type (WT) rats.
A proposed pathway for the protective effects of metformin against DM-induced disorders on atrial SK2 and SK3 channels
Mechanism model of PIK3CA E542K and E545K mutation-mediate regulation of proliferation and glucose metabolism via the β-catenin/SIRT3 in cervical cancer
Components of the phosphoinositide 3-kinase (PI3K) signaling pathway and its associated therapeutic targets
Schematic representation of canonical and non-canonical inflammasome signaling pathways.Notes: The figure describes both the canonical and non-canonical signaling pathways involved in the activation of different inflammasome components including NLRP1, NLRP3, NLRC4, and AIM2
The non-Smad-dependent pathway is predicted to be involved the changes of Cx43 but not in the present study
Nobiletin-induced apoptosis and suppressed migration and proliferation of human breast cancer cells via regulating p38 MAPK, NF-Œ∫B pathway, and Nrf2 pathway
The signaling pathway of defensins and interleukins gene expression is regulated by PBA in porcine intestinal epithelial cells
Potential CRC risk associated with metabolic incorporation of non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) from red meat
Hypothesied pathway showing the inhibitory mechanism of cyclin G2 on Wnt/β-catenin signaling through Dpr1
Proposed pathway of anti-tumor effects of propofol on lung cancer A549 cells
TREM2 molecular signaling in microglia, initiating phagocytosis and microglial survival or modulating proinflammatory response, is not well characterized so only validated components are displayed
Gene-level alterations in muscle-invasive bladder cancer in the context of curated pathways
Hierarchical representation of pathways in PASNet
Intrinsic and extrinsic apoptosis pathway
Transcripts shown in grey nodes contain GREs in their 3’UTRs
The Coagulation and Complement pathway is shown in this diagram, (source: https://www.wikipathways.org/index.php/Pathway:WP558.)
Cell survival and apoptotic pathway in AD therapy.Notes: Action of WGA-CRM-CL/LIPs: Curcumin inhibits phosphorylation of JNK and p38, preventing downstream phosphorylation of tau serine 202, leading to prevention of apoptotic neurodegeneration
Model proposing ROCK inhibition mediates morphological shift and neurite outgrowth-promoting property of OECs
String pathway enrichment analysis revealed strong associations (P=0.007) of the identified prognostic genes (colored nodes)
Scheme illustrating the signaling pathways and transcription factors contributing to SND1 promoter activation
Proposed mechanisms of anthocyanin’s effect on NVU dysfunction after ischemic stroke
Pathways involved in hyperglycemia-induced neuroinflammation
A schematic diagram of FOXO1-mediated miR-3188-mTOR-p-PI3K/AKT-c-Jun signaling feedback loop in NSCLC
The TNF-bound TNFR1 is shown with the formation of complex I, leading to NF-κB activation on the left side, and formation of complex II, leading to cell death, on the right side
The bait proteins are represented by blue nodes
Central metabolic pathway of representative carbon sources in model iZBM1060 (detailed information on enzyme information and reactions are presented in Supplementary Table )
Constitutive Wnt/β-catenin signal activation is common in human osteosarcoma while activating genetic mutations of Wnt pathway components in osteosarcoma are rare
Schematic illustrating the potential contributions of ADAM9 (a disintegrin and metalloproteinase domain-9) to various chronic obstructive pulmonary disease phenotypes
The IL-20 receptor cytokines and their receptors
Schematic molecular mechanism of LPA's effects on ion channel regulation
Overview of neuronal signaling events that influence miRNA biogenesis, activity, and degradation
Proposed roles for miR-137 at the glutamatergic synapse
Schematic representation of Tankyrase-mediated Wnt/β-catenin signalling
Canonical pathway analysis using MetaCore identified EGFR, PDGFR, and mTOR signalling as the top 3 canonical pathways modulated in FCD type II patients
Schematic of the activation of Wnt/β-catenin signaling by different oncogenic lncRNAs in liver cancer
Affected pathways in SHH-activated medulloblastoma
The consequences of driver gene mutations in canonical Wnt signaling
Affected pathways in group 4 medulloblastoma
The HOG and PKA pathways collaborate to regulate glycogen and trehalose metabolism for cell wall polysaccharide precursor biosynthesis during osmotic stress conditions
Adipocytokines mediate pancreatic cancer tumorigenesis by different signaling mechanisms
Altered gut microbiota is responsible for pancreatic cancer progression
Mechanism of HSV evades host immune responses
Modulation of oxidative status and leptin signalling pathway in human mammary epithelial cells
Inactivation of the Hippo pathway induces breast cancer metastasis
E3 ligases regulate breast cancer cell proliferation
E3 modulate breast cancer cell invasion and metastasis
An involvement of reactive oxygen species in intracellular signaling
Overview of egg activation in Drosophila
The schematic graphic of the mechanism underlying chondrogenesis driven by PC nanofiber membranes
Cardiac metabolic alterations in heart failure
Comparison of four TPs in breast cancer subtypes
The role of cav-1 in angiogenesis and neurogenesis
Schematic illustrating the role of cav-1 in different cell
Information processing by the NF-Œ∫B pathway
A descriptive model for the signaling pathway of nNOS in excitatory neurons
Molecular mechanism(s) underlying the abnormal GABAAergic system in HD
The putative mechanism is demonstrating how the loss of SEMA5A can trigger EMT
Proposed mechanism for tobacco smoking-mediated E6/E7 overexpression
Distribution of target proteins of SBD on the compressed ‘NSCLC-pathway.’ Four pathways form the tubular NSCLC pathway
Hypothetical model of anti-HBV mechanism of TLR3 signaling of HSCs
Examples of in vitro molecular action of quercetin (Q) in cited cellular experiments
The reprogramming of metabolism in cancer involves positive feedback loops with metabolic outputs such as amino-acids, lactate, and ATP serving as stimuli of the signaling pathways, which are in turn driving the upstream regulators of metabolic enzymes [–]
Schematic of DMN-induced liver fibrosis through activating the TGF-β/Smad signaling pathway and GA attenuate liver fibrosis through blocking Smad phosphorylation in liver cell
General representation of the signaling pathways involved in CBD anticancer mediated effects
Plant metabolic orientation of hormone interplay, carbon partitioning and responses on mycorrhizal development under low available P
Plant metabolic orientation of hormone interplay, carbon partitioning and responses on mycorrhizal development under high available P
A general overview of the autophagic pathway and its regulators
FSIP1 silencing promotes autophagy by releasing ULK1 from the FSIP1–ULK1 complex and causes chemoresistance through AMPK activation, Wnt/β-catenin pathway inhibition, and reduction in cell proliferation and migration, thus regulating the survival of TNBC
Summary of the Ras/MAPK cell signalling pathway and relation with some syndromes (nonexhaustive)
Enhanced glycolysis in cancer cells, through a combination of metabolic pathways, drives glucose utilization to fulfill high anabolic demands
displays the JAK-STAT signaling KEGG pathway as well as the miRNAs found to be associated significantly with the mRNA
In the TME, APCs present tumor antigens to naïve T cells and induce T-cell activation
Overview of the glucose catabolism pathways and transport systems of strain A4B-17
Summary of the interactions between SIRT1 and the canonical Wnt pathway
Mechanisms of hepatitis C virus-induced inflammation
ADAR1-mediated RNA editing in cancer development
ADAR2-mediated RNA editing in cancer development
ADAR1-mediated RNA editing in metabolic disorders
ADAR2-mediated RNA editing in metabolic disorders
Signaling pathway analysis of KEGG and PANTHER pathways shows that the miR‐34a/BCL‐2 axis is mostly involved in apoptotic pathways
Pentraxins-expanded network of complement activation and regulation
IL-6 mediated drug resistance in RCC cells
Schematic diagram of the anti-inflammatory mechanism of bicyclol
Abnormalities in the DNA damage repair pathway in T cells of rheumatoid arthritis patients
Regulation of CFTR by the intracellular Ca2+
Metabolic pathway of lipid metabolism in muscle
Possible molecular targets of the preventive effects of PT in Cr(VI)-induced ACD
CircRNA-miRNA interactions are potentially involved in the initiation and progression of CRC
NF-Œ∫B signalling pathway is involved in endogenous DcR3 expression in HUVECs stimulated by LPS, LTA and zymosan
Schematic of FGF and VEGF signaling network
Sagittal representation of the mesocorticolimbic system and the brain stress-related areas
The general mechanism of the extracellular signal-regulated kinase (ERK) pathway and key downstream products important in cocaine addiction
The Hippo Pathway and its canonical upstream regulators
KIBRA/Hippo pathway as a shunt of stressful input
Molecular pathways that play central roles in mounting an immune response in C
TGF-β upregulated miR-21 inhibits cancer cell apoptosis via posttranscriptional repression of proteins such as MSH2 and PDCD4, which are known to induce apoptosis, whereas miR-494 upregulated by TGF-β promotes proliferation of cancer cells
Dissection of the apparent clearance (CL/F) formula to describe all possible influencing parameters
Beclin 1 as a switch between homeostasis and apoptosis in neurodegeneration
a Qualitative Biological Regulatory Network (BRN) of Hexosamine Biosynthetic Pathway (HBP) intersection with PI3K-mTOR-Myc signaling and P53-MDM2 signalling axis
A simplified model of the molecular pathways by which pazopanib and AR42 combine to kill cancer cells
A simplified model of the molecular pathways by which neratinib and valproate combine to kill cancer cells
The pathway of YAP signal from KEGG pathway database
A proposed conceptual model for the regulation and function of locust Na+/K+-ATPase in JH-stimulated Vg uptake and oogenesis
Proposed model of LUBAC-mediated ubiquitination on cFLIP in the TNFŒ± receptor signaling pathway
Proposed scheme of nutmeg action in soleus muscle
The result of newborn mouse lens epithelial cell
. Potential therapeutic targeting of Th22/IL-22 signaling pathways in AD.
Summary of five hypothetical pathways of Fusobacterium nucleatum (Fn) in promoting colorectal carcinogenesis: (i) FadA in Fn promotes chronic Fn infection of colon mucosa that triggers reactive oxygen species (ROS) and proinflammtory mediators; (ii) Fad2 activates β- catenin signaling that, through the Wnt signaling pathway, results in increased miRNA and NF-Œ∫B, and ultimately increases tumor proliferation; (iii) Fap2 interacts with TIGIT on natural killer (NK) and T cells to suppress immune response and promote tumor growth; (iv) Fn through Fap2 may recruit tumor-infiltrating myeloid cells; (v) Fn in conjunction with other microbiota may affect the production of Aryl hydrocarbon receptor (AhR) ligands
Main flowering time pathways acting in Arabidopsis thaliana: Photoperiod (orange and yellow), ambient temperature (red), age (green), gibberellins (brown), autonomous (sky blue), vernalization (light blue)
The dynamic gene expression profiles of CIK cells involved in the cell cycle and the natural killer cell–mediated cytotoxicity pathway
Immunological pathways targeted by the main novel therapies for IBD
Metabolic pathways controlling macrophage activation states
Overview of proposed PD-1 & PD-L1/L2 intra-cellular signaling between T cells and/or macrophage/monocytes, among others (e.g
Pathway analysis graph of G1/S checkpoint
APLNR(s) in representative vertebrate species
Autophagy, Keap1 and p62 regulate Nrf2 in HCC
Intermediary thiol metabolism in renal proximal tubular cells
The regulation of the Hippo/YAP signaling pathway in malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC)
Intestinal uptake of non-heme iron and its regulation
Transforming growth factor-β 1 (TGF-β1) mediates a signaling pathway in tissue fibrosis
Illustrative fluxes in central metabolic predicted by geometric FBA for each growth condition: Control (black), NO3−-limited (NO3−, blue), PO43−-limited (PO43−, green) and SO42−-limited (SO42−, orange)
Links between Lipid and Iron Metabolic Pathways
Relationship between mechanical loading and sclerostin expression
Graphic representation of the hepatic Hepc pathway in conditions of systemic iron increase
Transient receptor potential (TRP) channels and itch signaling
Phosphorylation of DLP1 and their effects on mitochondrial morphology and mitochondrial and cellular functions in cardiomyocytes
An overview of the simple central carbon network of the Xanthomonas oryzae pv
Major mechanisms for hepcidin regulation
Mechanisms of Hedgehog pathway activation in cancer
NCOA4-mediated ferritinophagy pathway is regulated by intracellular iron
KEGG pathway analysis of the cell cycle in GNP-treated cells
Schematic diagram of the neuroprotective mechanism of action of xyloketal B in ischemic condition
Proposed anti-apoptosis mechanism for UDCA cardioprotection against hypoxia
In canonical Wnt pathway, DVL promotes clustering of Wnt-LRP5/6-Frizzled to form signalosomes, which results in phosphorylation of LRP5/6 and recruitment of Axin to the plasma membrane, further stabilizing the β–catenin levels in the cytoplasm
. Di-(2-ethylhexyl) phthalate (DEHP) induce apoptosis of cerebellar granule cells (CGCs).
Schematic depicting the proposed hypothesis that resistance exercise-induced adaptations may require the Hippo pathway effectors YAP and TAZ
DR and DR mimetics improve gut epithelial function
Schematic diagram of the suppressive effects of P
Status of proteins that participate in the autophagy pathway in glioblastoma
Visualization of DEGs involved in the mitogen activated protein kinase (MAPK) signaling pathway
The Drosophila Jak/STAT signaling components and the corresponding human homologs and their protein families
S100A10 plays a key role in regulating pro-tumorigenic processes including proliferation, adhesion, motility, invasion, metastasis, and therapy resistance
Summary of the proposed mechanisms of maternal cognitive impairment associated with gestational diabetes mellitus (GDM)
Schematic representation of canonical Wingless-type mouse mammary tumor virus (MMTV) integration site (Wnt) pathway and non-canonical Wnt/Ca2+ and Wnt/planar cell polarity (PCP) pathways [,,,,,]
Schematic illustration of Wnt1/β-catenin signaling regulation of midbrain dopaminergic (mDAergic) neuron survival/death according to our published findings [,,,,,,,,]
Schematic illustration of Wnt1/β-catenin signaling as a key player in glia–neuron cross-talk
TNF-α receptors, pathways and different types of signals—schematic diagram
Many molecules regulate apoptosis and Hippo-YAP signaling pathway
A simplified representation showing the interplay between the major signaling cascades activated by tyrosine kinase receptors (RTKs) and TSH-Receptor (TSH-R)
Schematic overview of RAS and PI3K pathway and their interconnection
Schematic depiction of the TGF-β signaling pathway
Schematic representation of the polyphenols’ major mechanisms of action on colorectal cancer (CRC) cells
Schematic representation of the non-polyphenolic compounds’ major mechanisms of action on CRC cells
Scheme of the main steps for autophagy and their regulation by AMPK
Expression of Insulin/IGF signaling components is modulated by miRNAs
Schematic diagram of hypothesized mechanism of S5-induced death of human melanoma A375 cells
mRNA translation stress feedback to ribosome biogenesis and cell proliferation
A) Several biochemical mechanisms that regulate YAP proteins, as described in the text, are shown
Transcriptomic analysis of axon guidance signaling pathways in liver fibrogenesis
Inhibitors to specific mechanical and metabolic pathways
Schematic representation of FGFR1/FGF21/βKlotho complex actions in the cardiomyocytes
Different signaling pathways related to EGFR activation induced by CTGF/EGFR interaction
Core metabolic pathways for T cell survival, activation, differentiation, and function
A variety of factors control Tn cell survival and metabolic pathway engagement after T cell activation
Proposed mechanism for ASIC1a regulation of striatal synaptic remodeling and motor learning
The chemical structures of the clinical indenoisoquinoline derivatives, LMP400, LMP776 and LMP744 are shown at the top left
Overview schematic of the proposed relationship of inhalant organic dust exposures induction of bone loss
A. The Mechanistic relationship between PI3K pathway activation and cell-cycle in tumor cells: PI3K signaling engages AKT, which drives mTORC1 CAP-dependent mRNA translation encoding CYCLIN D1/D2/D3.
Integrative Modeling of Cancer-Type-Specific Hippo Regulatory Networks
Potential role of MAIT cells in spondyloarthritis (SpA)
Ionizing radiation leads to the release of tumor associated antigens (TAA) and damaged DNA that can stimulate the production of type-I interferon via the cGAS/STING pathway in tumor cells
Environmental enrichment largely prevented age-SNCA-dependent disturbances and activated topologically relevant genes in the SNCA interactome with respect to both disturbance modes
Molecular pathways modulating lifespan via control of the translation machinery
Schematic overview on a striatal medium spiny neuron synapse
a | The DNA methylation cycle of cytosine nucleotide bases is depicted
a | Repressive histone-modifying enzymes Polycomb complex protein BMI1 and histone-lysine N-methyltransferase EZH2, as part of Polycomb repressive complex 1 (PRC1) and PRC2, respectively, contribute to the functional phenotypes of memory-like killer cell lectin-like subfamily G member 1 (KLRG1)–CD8+ T cells and terminally differentiated KLRG1+CD8+ T cells via subset-specific activity
The mechanism of CHOP regulation in ER stress induced apoptosis
Role Of Atm In Ebv Life Cycle Regulation (A) The central role of ATM in th... (B) ATM is regulated by EBV durin... (C) Potential involvement of ATM...
a) During infection, both the alternative and c... b) N. gonorrhoeae is able to survive in and aro... c) N. gonorrhoeae infection does not generate i...
Neurotrophic-tropomyosin receptor tyrosine kinase (NTRK) receptor signaling pathway and inhibitors
Sortilin and SorLA regulate IL-6 family signaling
The cellular functions and mechanisms of rapamycin
Rapamycin inhibits the de-differentiation of vascular smooth muscle cells
Cardiac and macrophage inflammatory pathways
Cartoon depiction illustrating potential saturated free-fatty acid mechanisms that may underlie arrhythmogenic events
DSBR pathways and the effect of RAD51 paralog loss on pathway choice
CTRP1 expression increases in response to glucocorticoids under dehydration conditions in skeletal muscle
The effects of different stent techniques on angiogenesis
Interferon (IFN)-dependent IFN stimulated gene (ISG) transcription through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling
IL-6 signaling in the tumor cell of the bone marrow niche
The role of cell-intrinsic PD-L1 in modulating signaling pathway
Signaling pathways activated after binding of E2 and G1 to GPER
Activating MAPK Pathway Mutations in LCH
Ingenuity pathway analysis (IPA) Core Analysis downstream effects depicts protein enrichments within our total retinal phosphoproteome across the top five retina-specific components of a larger network of proteins categorized within IPA under “Ophthalmic Disease”
Three mechanisms of pexophagy in mammalian cells
Signaling network regulating sodium-potassium-chloride cotransporter (NKCC2) and Na/H exchanger (NHE3) in thick ascending limb (TAL) cells
Simplified signaling pathway for vasopressin-mediated sodium-chloride cotransporter (NCC) regulation in distal convoluted tubule (DCT) cells
The mechanistic target of rapamycin (mTOR) signaling network
DEPTOR [Dishevelled, Egl-10, and Pleckstrin (DEP) domain-containing mTOR-interacting protein] as a tumor suppressor
ANG II induces cardiac hypertrophy by multiple means involving direct actions on cardiac myocytes (cm) or the release of paracrine factors from other cell types, such as endothelial cells and fibroblasts/myofibroblasts
Renal ion regulation in response to ANG II
A simplified representation of the complement system, divided into pattern recognition molecules (PRMs), pathway specific and common components as well as inhibitors
The three main features (GSIS, beta cell mass and insulin action) and insulin secretion pathway in GK rat
Epigenetic regulation at the RUNX3 AS-associated locus
Interplay between mTOR, Aβ and Tau in Alzheimer's disease
Therapeutic approaches in Alzheimer's disease: GSK3 Inactivation therapy: Neuroprotective compounds such as curcumin modulates PI3K/Akt/GSK3β pathway, leading to inactivation of tau hyperphosphorylation
Network displaying key genes involved in apoptosis, DSB repair, Fanconi anemia pathway and homologous recombination
Human oncogenic viruses modulate signal transduction pathways that control cell growth, proliferation and survival to optimize cellular conditions for viral replication, virion assembly and autophagic evasion in the absence of growth or survival signals
A model showing the possible pathways of neuropeptide Y-induced neuroprotective effects in Alzheimer's disease
Summary of the mechanisms involved in the stimulation of brown adipogenesis, mitochondrial biogenesis and energy expenditure by some dietary molecules
Schematic diagram of mechanisms for human cervical epithelial cells (HCEs)-mediated HIV suppression in macrophage
Methionine sets up a hierarchical metabolic response leading to anabolism
The mechanisms of S6K1 inhibitors-induced feedback activation of the PI3K pathway and insulin receptor sensitization
SNO profile of cell death network in Chagas disease (ChD)
SNO profile of inflammation and immune responses network in Chagas disease
. The role of CsA in the attenuation of morphine tolerance.
The cytokines, receptors, JAK and STAT complexes formed are indicated
There are two major pathways contributing to NAD synthesis: de novo synthesis and salvage from precursors
The mechanism of IL-22, IL-22receptor as well as IL-22BP and signaling pathway
Schematic figure for sildenafil-mediated apoptotic sensitization pathways
B-cell receptor (BCR) signaling pathways important to the pathophysiology and treatment options for chronic lymphocytic leukemia (CLL)
(A) An example of a reaction in our model for hypothetical PathwayX, whi... (B) Signal transmission route of “glucose” and “no glucose” conditions t...
Schematic of the signaling pathway implicated in VIDD development
Interconnection between LXRs and AR in prostate cell.Note
Summary of the oncogenic pathways genetically disrupted in the UM-SCC oral cavity cell line panel
Implementation of metabolic engineering strategies in S
Schematic/proposed signaling model in a cell during tumor formation
Schematic/proposed signaling model of role and regulation of claudins in a cell during invasive or metastatic stage
Schematic overview of major enzymes and metabolites involved in the regulation of gluconeogenesis
Hepatic gluconeogenesis is modulated by histone deacetylases (HDACs)
Signaling pathway and GO analyses were performed to identify the biological functions of the subsets of differentially expressed genes after BP5 treatment
Schematic representation of the processes underlying the proposed hypothesis of the temperature and CO2 effects on isoprene synthesis
The receptor for advanced glycation endp ro ducts (RAGE) is akey pathway for inflammatory complication sinaging and chronic disease
Pathway representation for dopamine metabolism
The proposed pathway of RSK related genes
Current strategies (blue boxes) and possible future strategies (red boxes) for enhancing or repairing the autophagic defects described in different neurodegenerative disorders
Microbiota and the intestinal barrier against infectious threats
A summary of interactions between ECM remodelling and kinase activity
(a) Schematic Representation of DDR1-collagen signaling pathway in cancer
Oncogenic and tumor suppressive signaling involving Dmp1 and Arf
TRAIL binds to its cell surface receptors DR4 and DR5 as a trimer
Cdk5 regulates actin dynamics by phosphorylating multiple upstream regulators (left panel) and downstream targets of Rac GTPase (right panel): Similar to RhoA, Cdk5 can either activate or inhibit the Rac1 pathway using alternate substrates, thereby controlling both actin polymerization and depolymerization
Relationship between NFŒ∫B and autophagy
Relationship between the downregulation of PTEN and autophagy
Relationship between the overexpression of YY1 and autophagy
Downstream effectors and upstream regulatory pathways of RKIP
Exogenous pathway of lipid metabolism.apo B-48 = apolipoprotein B-48, apo C-II = apolipoprotein C-II, TG = triglyceride, apo E = apolipoprotein E, LPL = lipoprotein lipase
Endogenous pathway of lipid metabolism.HDL = high-density lipoprotein, apo A = apolipoprotein A, apo C-II = apolipoprotein C-II, apo C-III = apolipoprotein C-III, apo E = apolipoprotein E, VLDL = very-low-density lipoprotein, CE = cholesteryl ester, apo B-100 = apolipoprotein B-100, LPL = lipoprotein lipase, PL = phospholipid, IDL = intermediate-density lipoprotein, LDL = low-density lipoprotein
Intercellular and intracellular signals that initiate liver regeneration
Role of PAK signaling in response to inflammation, altered microbiota and hyperglycemia
Schematic representation of protein synthesis and degradation pathways in skeletal muscle
Scheme illustrating the downstream signaling of the HER pathway, chiefly the mitogen activated protein kinase (MAPK)/ERK pathway, the phospholipase Cγ (PLCγ) pathway, the signal transducer and activation of transcription (STAT) pathway, and the phosphoinosidyl-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway; where ER=Endoplasmic Reticulum, Ca2+=Calcium ions
In this model, β-adrenergic receptor stimulation of adenylyl cyclase (AC) generates pools of cAMP that are differentially regulated by PDE2 and PDE3
Potential molecular signaling mechanisms of nicotine mediated anti-inflammatory effects
Several signalling lipids, including fatty acids, fatty acid esters of hydroxy fatty acids (FAHFAs), diacylglycerol (DAG) and ceramides, regulate intracellular pathways to influence insulin resistance
Proposed model for the cross-talk between HGF/c-Met and SphK1/S1P/Spns2/S1P1 signaling axis in HGF-mediated lamellipodia formation
FOXO activity, stability, and localization are regulated by the insulin/IGF signaling pathway and reactive oxygen species
NF-Œ∫B and IRF3 signaling pathway regulation by miRNAs implicated in inflammatory diseases
Ingenuity Pathway Analysis (IPA) network map depicting the DR signaling changes in HBEpCs after 2 h of infection with IAV H1N1
IPA network map depicting the DR signaling changes in HBEpCs after 6 h of infection with IAV H1N1
Simplified illustration of TXNIP role in presumptive pathways involved in endothelial dysfunction
The genes and their functional relationships within the RLR signaling pathway
IBD pathway, red nodes indicate genes differentially expressed in AUC or EUC
The analysis of the SMARCB1 wild type and the R377C mutant led to the identification of 52 altered HCIPs
Schematic of the HMG‐CoA (3‐hydroxy‐3‐methylglutaryl coenzyme A) reductase pathway
Statins and prenylation inhibitors in Marfan syndrome aneurysm development: hypothesized model
The drawing represents a composite model derived from references–, although further studies will be necessary to fully understand the architecture of the Shieldin complex
T cell activation induces cell surface expression of GLUT1 and amino acid transporters, facilitating uptake of glucose and glutamine
Proposed bioflocculant (BF) synthetic pathway and the genes of Citrobacter freundii IFO 13545 involved in the pathway
G-protein mediated effects on smooth muscle tone regulation
Nutrient deprivation and organelle damage trigger macro-autophagy in cardiac myocytes (reviewed in ())
Various cell-intrinsic and extrinsic inputs regulate the autophagy-lysosome machinery
Expanded cholesterol synthesis pathway diagram
cGMP-mediated modulation of IOP through increase in AqH outflow
Signaling pathway for p38γ MAPK-promoted EMT
EMT is Modulated by Multiple Cascades Through Several Networks
Probing dynamic signal transduction and filtering in cancer cells
The different subcellular sources of MHC-I molecules for cross-presentation
Convergence of three vesicular pathways of endocytic traffic on the cross-presentation compartment in dendritic cells
Proteins that Are Rhythmic in the Pentose-Phosphate Pathway Peak in Anti-phase to Those in Glycolysis
Proposed mechanism of osteopontin (OPN) stimulated monocyte chemoattractant protein 1 (MCP-1) production and migration of monocytes
Shortcuts on a black background indicating the mine enzymes: AHAS, acetohydroxyacid synthase; BCOADH, branched chain 2-oxoacids dehydrogenase (E1 component of branched chain 2-oxoacids dehydrogenase complex); DXPS, 1-deoxy-D-xylulose 5-phosphate synthase; OGDH, 2-oxoglutarate dehydrogenase (E1 component of 2-oxoglutarate dehydrogenase complex); PDC, pyruvate decarboxylase; PDH, pyruvate dehydrogenase (E1 component of pyruvate dehydrogenase complex); TK, transketolase.Gray asterisk – metabolites directly associated with thiamine pyrophosphate-dependent pathways.Thiamine diphosphate-dependent enzymes play a role in photosynthesis in chloroplasts (TK, DXPS), pentose phosphate pathway (TK), and alcoholic fermentation (PDC) in cytoplasm as well as in ATP synthesis by participation in oxidative decarboxylation of pyruvate (PDH) and Krebs cycle (OGDH) in mitochondria.
Pink color represents the core circadian genes, red color represents the miRNAs and blue color represents the miRNAs targeting genes related to hippo signaling pathway
MAPK pathway is important signaling pathway that is activated in response to various stress stimuli
a |Schematic illustration of a systems biology approach for identifying novel genes likely to affect spine plasticity in neuropsychiatric disorders
Within the dendritic spine, AMPA receptors (AMPARs) govern fast synaptic transmission in response to glutamatergic signalling
DNA sensors and related signaling pathway
Schematic model in which HMW FGF2-mediated FGF23 stimulation of chondrocyte differentiation and OA is partially through modulation of the Wnt/β-catenin pathway
Macrophages populating the atherosclerotic plaque express high surface density of the immuno-inhibitory ligand PD-L1 and suppress the induction of T-cell responses
In the kynurenine pathway, tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase convert tryptophan into N-formyl-L-kynurenine, which is further metabolized to L-kynurenine by formamidase
Signaling Cascades leading to contraction in lymphatics
Interactive signaling pathway of EGFR-PI3K-mTOR
DNA repair pathways—a toolkit for viral replication
Signaling downstream of the IL-2 receptor (IL-2R)
Ligand binds to and activates its membrane-bound G protein-coupled receptor (GPCR) leading to the dissociation of the GŒ±,s subunit from the GPCR
Schematic illustrating the polyamine metabolic pathway in human cells
Iron depletion leads to: (1) alterations in the expression of c-Myc and p53, where iron-depletion decreases c-Myc expression in both cell-types, while decreasing expression of mutant p53 (SK-Mel-28) and increasing wild-type p53 (MCF-7); (2) changes in the expression of polyamine pathway proteins involved in catabolism/efflux and biosynthesis/uptake (increased protein expression is marked by red arrows, while decreased protein expression is marked by blue arrows); (3) conserved alterations in the expression of polyamine pathway proteins in SK-Mel-28 and MCF-7 cells, some of which are downstream of the changes in c-Myc and p53; (4) decreases in key polyamine metabolites, AdoMet and spermine, in SK-Mel-28 cells; and decreases in AdoMet, spermidine and spermine in MCF-7 cells; and (5) decreases in proliferation, which can be partially rescued by supplementation with putrescine and spermidine
a | Arginase 1 (ARG1) produces ornithine from the amino acid arginine as part of the urea cycle
mTOR complex 1 (mTORC1) stabilizes pro-S-adenosylmethionine (AdoMet) decarboxylase (pro-AdoMetDC), leading to increased AdoMetDC and increased polyamine biosynthesis in prostate cancer
Force on E-cadherin triggers the recruitment LKB1 and the subsequent activation of AMPK
Schematic model for the roles of Lats1‚ÄêYAP1 signaling in neuronal apoptosis
Schema of multiple pathway targets in CRC described in the review
Receptor tyrosine kinase (RTK) signaling was subjected to BL-dependent optogenetic control as exemplarily illustrated for the MAPK/ERK pathway
Optogenetic control of phosphatidylinositol signaling
Proposed model of sepsis-induced thrombus formation
Network of Neurotrophin signaling pathway
Proposed mechanism of PQ cytotoxicity in marine NPCs
Selected genomic alterations are indicated by an asterisk (*): fibroblast growth factor receptor (FGFR) pathway (FGF19, FGF4, FGF23, FGF3, and FGF6 amplifications)
Lymphocyte specific functions via non-canonical pathways involving MST1/2 are shown
Myeloid cell specific functions via non-canonical pathways involving MST1/2 are shown
Adiponectin-mediated signaling pathway in HSCs
An increase in extracellular proteases and free radicals accompanied by a severe decrease in pH and follistatin activates myostatin/activin factors
The CaSR is functionally active as a constitutive homodimer, and may also form heterodimers with other family C GPCRs such as the metabotropic glutamate receptors and gamma-amino butryric acid (GABA) type B receptors in growth plate chondrocytes and the central nervous system–
Examples of axonal stress that lead to activation of DLK
Soluble amylin and pramlintide are capable of activating the endogenous AMYR which is responsible for recruiting adenylate cyclase
Menin-associated pathways with potential targeted therapies
Upon ligand binding (parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) are shown on the figure), the G protein coupled PTH/PTHrP receptor type 1 (PTHR1) activates the heterotrimeric Gs protein
(a) GTPase signaling: Rho-family GTPases regula... (b) Lipid patterning: The site of injury underg... (c) Potentiation of repair: Localized activatio...
The NF2 gene encodes the merlin protein, which regulates the Hippo pathway
Type I IFN plays an integral role in macrophage regulation of Mmp28 following stimulation with PAMP
The cancer-selective strategy to target the NF-Œ∫B signalling pathway
Schematics of cellular energy-generating pathways
Schematic representation of receptors and signaling pathways mainly contributing to anti‚Äêinflammatory polarization of microglia
Metabolic drugs and molecular pathways exploitable to drive microglia into a pro‚Äêregenerative phenotype
Examples of biosynthetic pathways of different classes of GLSs (A) Biosynthetic pathway f... (B) Pathway for chain‐elon... (C) Pathway for indolic GL...
Possible sex effects on aspects of the CR/Met R mechanistic pathways
Synthetic Biology Tools for Programming Cell and Tissue
Overview of Altered Metabolic Pathways in Glioblastoma
Outside-in and inside-out signal transduction in myofibroblastic activation
In aged endothelial cells increased levels of ROS generated by NOX oxidases (stimulated by elevated TNFŒ± levels and/or by the activated local renin-angiotensin system [RAS] in the vascular wall) and mitochondria decrease the bioavailability of NO by forming ONOO-
PI3K/Akt pathway plays a central role in nutrient-mediated cell proliferation and growth
WNT signaling must be inhibited in the foregut and induced in the midgut and hindgut for proper regionalization of the GI tract epithelium
A) Danio rerio Wnt signaling pathway. Colored stars used as in . B) Table of differentially expressed genes in the Wnt pathway and corres...
A) Danio rerio FGF signaling pathway. Colored stars used as in . B) Table of differentially expressed genes represented in the FGF pathwa...
a | In phagocytes and dendritic cells, stimulation of surface Toll-likereceptor 4 (TLR4) by lipopolysaccharide (LPS) or endosomal TLR3 by double-stranded RNA (dsRNA) results in activation of interferon regulatory factor 3 (IRF3) via a TIR domain-containing adaptor molecule 1 (TICAM-1, also known as TRIF)-dependent pathway, and nuclear factor-Œ∫B (NF-Œ∫B) via myeloid differentiation primary response protein (MyD88)
Schematic diagram representing possible antifungal mechanism (a–e) of CIN and EUG in C
Pathways that may impact radiosensitivity
Leptin binds to the LEPR and mediates multiple downstream pathways
Full candidate pathway that represents molecular drivers of tumorigenesis in the sarcoma of patient 1
TGFβ family members exhibit distinct effects on heart hypertrophy‚ÄÉTGFβ binds to its own receptors RII and RI, activates TAK1, SMAD2/3, and p38, and moderately promotes cardiac hypertrophy
TGFβ stimulates cardiac resident fibroblast-to-myofibroblast transition‚ÄÉStress-induced TGFβ release from the latent complex leads to the activation of membrane-bounds TGFβ receptor complexes, which induces Smad2/Smad3 and multiple non-Smad signaling pathways, including TAK1, MAPK/p38, and Rho-GTPase/Rock for activation of myofibroblast specific genes, such as Œ±-SMA, Col-I, Col-III, Postn
Schematic diagram illustrating a role of PI3K, Rho and ROCK pathways in hypoxia-induced ATP release and ATP-mediated angiogenic effects in vasa vasorum endothelial cells
β-catenin: immune exclusion mediated by activation of the WNT–β-catenin pathway occurs when expression of CC-chemokine ligand 4 (CCL4) is inhibited and thus basic leucine zipper transcriptional factor ATF-like 3 lineage dendritic cells (BATF3 DCs) are no longer recruited into the tumour microenvironment
Cross-talk between the CDK4/6 and mitogenic signaling pathways in cancer
Overview of metabolic reprogramming in CRC
Overview of metabolic pathways regulated during T cell differentiation
a | An illustration of our definition of canonical RB function is presented
a | Positive growth signals activate cyclin-dependent kinases (CDKs) to phosphorylate and inactivate RB, whereas negative growth regulators (DNA damage and transforming growth factor-β (TGFβ)) augment CDK inhibitors
LMP-1 rescues Smads from Smurf1-mediated proteosomal degradation
Aging negatively affects HSC function through both intrinsic and hematopoietic microenvironment mediated mechanisms
Schematic overview of cytoplasmic 60S subunit assembly
L-selectin binding to ligands causes selectin clustering, which induces receptor tyrosine and serine phosphorylation and activation of the ERM proteins
Cholesterol-dependent inflammatory response and cell death in the hepatocyte
In response to renal injury, resident renal cells and infiltrating immune cells produce a number of factors that initiate the processes of renal fibrosis, including TGF-β and ROS
Sex differences in the signal transduction pathways of endothelial nitric oxide (NO) synthase (eNOS) activation in endothelial cells by estradiol and testosterone and the subsequent vascular response
Fibrin and fibrinogen interact with receptors on nervous system cells to activate downstream signalling, regulate basic cellular functions and influence inflammatory, neurodegenerative and repair processes in disease,,,
Differentially expressed transcripts in FSGS were enriched in the JAK-STAT pathway in the tubulointerstitium
Differentially expressed transcripts in FSGS were enriched in the JAK-STAT pathway in the glomeruli
Model of hepcidin regulation by iron and erythropoiesis
Protein pathway analysis using serum proteins present in healthy controls and/or AA patients
Schematic overview of the two most common pathways with genetic alterations in thyroid cancer—mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinase (PI3K) pathways
General mechanism of SYK activation and SYK-mediated signaling: a pathway demonstrating the involving of downsignaling associated with SYK activation
Genes in the mitochondrial fatty acid oxidation (FAO) pathway that have been studied for links to T2DM
Novel insights into the dectin-1 signaling pathway
Crosstalk between different PRRs in antifungal immunity
PolyI:C enhances IgA production in the NALT via the TLR3-TICAM1 pathway
Schematic representation of important factors involved in the pathogenicity of septic shock caused by LPS from gram-negative bacteria
Metastasis models in Drosophila melanogaster have revealed that a variety of stresses activate the Jun N-terminal kinase (Jnk) pathway, which at high levels of signalling can lead to apoptosis
Metabolic pathways are fertile ground for therapeutic interventions in SLE
Schematic diagram of the signaling pathway regarding the cell cycle regulation in human bladder transitional carcinoma/BFTC-905 cells after stimulated by LSS
Brief description of the interaction of a CD4+ T cell with B cells
Schematic diagram of the NF-κβ pathway and the inhibitory effect of various alkyl nitrate N-Aryl Piperamide on NF-κβ translocation and COX-2 function
Proposed model for transcriptional regulation of TGF-β signaling pathway in D
Pathway analysis of predicted potential targets to combine with MAPK/ERK inhibition, using graph analytics
FGFR pathway and dysregulation in cancer []
The transfer of information from neurons to astrocytes, and the reverse process, are schematically separated by a dashed line
Associated cell signaling pathway and related potential therapeutic areas
Four hyperglycemia-induced pathogenic pathways which are related to overproduction of ROS and inflammation progression in atherosclerosis
Downstream products of ROS promote endothelial cells (ECs) dysfunction in atherosclerosis
Model illustrating the potential pathway from pseudohypoxia-induced cilia loss to increased cell proliferation and dysregulation of tumorigenesis relevant cilia-mediated signaling pathways in PCCs
The effects of DUSP5 deletion on oncogenic signalling through the Ras-ERK pathway may depend on the nature of the driving oncogene
Mechanistically distinct regulation of VEGF secretion in MDA-MB-231 TNBC and T47D (ER+/PR+/HER2-) cells
Pathomechanisms and clinical features of diabetic cardiomyopathy
Diagram summarising a critical role of ZEB1-tPA axis regulated by EGFR–RAS–ERK pathway in the development of lung fibrosis (details provided in Discussion)
Mechanistic aspects of the VHL-HIF-BNIP3 signaling pathway
Involvement of circRNAs in the ErbB signaling pathway
Involvement of circRNAs in the Hippo signaling pathway
Sonic Hedgehog (Shh)-dependent morphological, cellular and molecular alterations in the dentate gyrus (DG) of Ptch1+/– mice.Schematic model in which Shh pathway activation positively feeds into the activities of the Notch signaling pathway resulting in upregulation of TLX, a direct target of Notch1/recombining binding protein suppressor of hairless (RBPJ), positively regulated by Sex determining region Y (SRY) box 2 (Sox2) and overexpressed in the DG of Ptch1+/– mice
Schematic illustration of mTOR/S6K intracellular signal transduction pathways in the osteoclast
KEGG-defined p53 signaling pathway with dysregulated mRNA and miRNA highlighted
The Ras/ERK signal transduction pathway with emphasis on p120-RasGAP interactions
Putative relationship between changes in tryptophan catabolism and de novo NAD+synthesis in ADC neuropathology
Schematic diagram of the ERK/MAPK signaling pathway in liver metastasis of colorectal cancer regulating by PEA15
Molecules associated with ‘focal adhesion’ pathway
ECM stiffness rather than matrix adhesivity affects osteosarcoma cell growth through regulation of the integrin-mediated FA signaling pathway, whereas osteoblasts are mainly affected by ECM adhesion ligands through modulation of the integrin-mediated AJ signaling pathway
Schematic representation of the melanogenesis pathway shows where common ENAMs affect the pathway
MiR‐24‐3p regulates cell proliferation and milk protein synthesis in mammary epithelial cells through cooperatively acting with MEN1/menin
Retinoic acid signaling pathway within a cell
Decorin in cancer, based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (http://www.genome.jp/kegg‚Äêbin/show_pathway?hsa05205)
The effect of changes in ECM‚Äêmediated signalling pathways
Signaling pathways by which NPs induce apoptosis
Autophagy signaling pathways induced by NPs
Model for signaling in HIV-1-mediated inflammation
Structural landscape of druggable proteome in oncology drug discovery
Fibrocytes originate from monocyte progenitors and migrate to fibrotic lesions of injured lungs to secrete paracrine factors that can cause fibroproliferation and fibroblast-to-myofibroblast (FMT) transformation in the pathogenesis of pulmonary fibrosis
Proposed mechanisms of nitrergic neurotransmission in the SIP syncytium
IL3 is a cytokine that regulates the growth and differentiation of hematopoietic cell populations
Schematic depicting the proposed molecular mechanism by which citrate regulates cellular redox signaling pathways in BMSCs
A schematic view of the signalling transduction pathway of isoflurane (ISO) cardiac preconditioning
Leptin regulates fatty acid oxidation in muscle by activating AMPK
GnRH-stimulated signaling pathways that regulate Fshb gene expression
Metabolism of fuel substrates drives the levels of reduced equivalents (NADH and NADPH) in normal cardiomyocytes
The four main redox couples governing the redox balance in cardiac mitochondria (NAD+/NADH, NADP+/NADPH, GSH/GSSG, and TrxSH2/TrxSS) are hinged by NNT
Maintenance of mitochondrial and extramitochondrial NAD pools
The JAK/STAT pathway is involved in the miR155/SOCS1 axis in the immune system
Role of the NF-Œ∫B pathway in the miR-155/SOCS1 axis in the immune system
Crosstalk between the Rho kinase and BMP-2 signaling pathways
The pathways participate in tumourigenesis of CCA
The RAS/ERK, PI3K/AKT, WNT and β-catenin signaling pathways are involved in different stages of brain development and are commonly disrupted in ASD
Simultaneous inhibition of the glycolysis and the glutathione and thioredoxin systems reduces cancer cells’ defenses against reactive oxygen species, and can be used as a strategy to sensitize cancer cells to therapies that increase oxidative stress, like radiation therapy
FLNA bound R-Ras can be activated through various receptor engagements (including TGFβ as depicted) leading to MAPK pathway activation of Erk1/2
Signalling pathways related to PRL-3/EGFR/c-myc genes in cancer cells
Schematic representation of TGF-β signaling as well as the role of TGF-β signaling pathway in cancer onset and progression
Roles and regulation of PAH1-encoded PA phosphatase in lipid synthesis
Cell cycle timing and regulation of replicative histone genes
ProQ-dependent changes in Salmonella-infected HeLa cells
Targets molecules of bta-mir-182 involved in the apoptosis signaling pathway
Differentially expressed genes connected to electron transport chain pathway
miR-30e inhibits adhesion, migration, invasion and cell cycle progression of PCa cells via suppressing CHRM3 expression and activation of the MAPK signaling pathway
Model for the regulation of major histocompatibility complex class I (MHC‐I) expression in non–small cell lung cancer cells by epidermal growth factor receptor (EGFR)‐MEK‐extracellular signal‐regulated kinase (ERK) signaling
General molecular mechanisms of metformin on inhibiting cancer cell growth
Mechanisms of metformin combined with Abs or small molecular inhibitors in cancer treatment
Wnt signaling pathways and the intervention targets of Wnt pathway inhibitors
Current model of iron sensing in the liver to regulate hepcidin production
Characterization of complex transporter-mediated model of carbon allocation and energy supply for oil synthesis in developing P
Proposed mechanism for kCer acting as a Sema3A-like ligand
Diagram of knockdown of TFPI-anchored endothelial cells induced a more severe LPS-induced acute lung injury via NF-Œ∫B signaling pathway
Expression ratios representing the changing abundance of 237 bone-related mRNA species in MC3T3-E1 cells between days 2 and 5 in culture were used to populate the IPA osteoarthritis pathway network and signaling pathway activation state was assessed using the IPA molecular pathway predictor tool
Expression ratios representing the changing abundance of 237 bone-related mRNA species in MC3T3-E1 cells between days 5 and 10 in culture were used to populate the IPA osteoarthritis pathway network and signaling pathway activation state was assessed using the IPA molecular pathway predictor tool
Expression ratios representing the changing abundance of 237 bone-related mRNA species in MC3T3-E1 cells between days 10 and 28 in culture were used to populate the IPA osteoarthritis pathway network and signaling pathway activation state was assessed using the IPA molecular pathway predictor tool
Schematic model depicting the proposed signaling pathway in LH/hCG-induced the resumption of meiosis
Simplified reference TLR signaling pathway projected onto putative homologs in Trichoplax sp
Putative Celangulin V biosynthetic pathway in C
Autocrine/paracrine effects of FGF23 in FGF23-producing tumor cells.Membrane-bound Klotho enables the autocrine and paracrine effects of FGF23
The stalling of replication forks is sensed as replication stress and leads to the exposure of ssDNA, which is recognized by RPA
Proposed model for CK-mediated anti-inflammatory activity by targeting AKT1 in NF-Œ∫B signaling pathway during macrophage-mediated inflammatory responses.MAPKK, mitogen-activated protein kinase kinase; MAPK, mitogen-activated protein kinase; IKK, IkBa kinase; TBK1, TANK Binding Kinase 1; AKT, protein kiase B
Overview of the proteome changes in (A) G-protein signaling pathway, (B) calcium signaling pathway and (C) ginsenoside synthesis pathway and (D) ribosomes biogenesis, ubiquitin-mediated proteolysis and RNA transport pathway
Underlying regulatory mechanisms of CCAT1 in human cancer
Different stages of erythropoiesis and regulatory processes (including cytokines, transcription factors and related signal transduction proteins)
PI3K/Akt signaling pathway and glucose metabolism (glycolysis, glucose uptake, nitric oxide glucose synthase, apoptosis and cell survival)
Schematic presentation of the proposed effects of melatonin against ANIT-induced intrahepatic cholestasis
Differentially expressed genes (DEGs) associated with plant-pathogen interactions in H
(A) The MAPK (ERK) signaling pathway in the KEGG pathway map (hsa04010)... (B) An example of the network variation map (nt06201) as a collection of...
. Patient clinical pathway of a clinical study.
Pathway by which starvation induces a glucagon-mediated increase in liver autophagy
Optotherapeutic strategies: several optogenetic implants have already been tested in mice and proved to be functional to treat diabetes as well as erectile dysfunction
Mechanisms underlying the loss of primary cilia frequently observed in cancer cells with aberrant RTK
Schematic diagram showing PR/RANKL pathway and downstream RANK-mediated signaling in mammary epithelial cells
Central carbon and γ-PGA production pathways of B
Schematic illustration of the proposed cardioprotective mechanism of mAb A treatment in hearts following a myocardial infarction
Schematic model of the interaction between reprogramming to pluripotency and tumorigenesis
Schematic model for the possible E2 uptake pathways in leukocytes
Schematic of the ubiquitylation of glycoprotein (GP) VI signalling pathway
Classes of drugs that modulate the cGMP-PKG pathway in relation to SERCA2a within cardiac myocytes (cardiomyocytes)
LPS-TLR4-NFŒ∫B signaling pathway is an established potentiator of TNFŒ±-dependent inflammation in metabolic disorders
Dacarbazine and PLX4032 cross-resistance emerges via distinct MAPK-dependent and -independent pathway activation
HA interacts with the ectodomain of the CD44v6 molecule to facilitate CRC colonization, invasion, and metastasis
After binding to the ectodomain of the CD44v6 molecule, OPN is potent in inducing CRC colonization along with invasion and metastasis
As a signal integration platform, the ectodomain of the CD44v6 molecule can be bound with several cytokines, such as EGF, HGF, VEGF, and CXCL12, which are known to be potent in inducing cell proliferation, anti-apoptosis, migration, and angiogenesis through activating MAPK/ERK signaling pathway (red line) and PI3K/Akt signaling pathway (yellow line) after binding with their receptors
a CD44v6 is able to increase the resistance of CRC cells to apoptosis
a The strategy of anti-CD44v6 therapy by blocking the interaction between HA and CD44v6
MicroRNA-146bb induces the PI3K/Akt/NF-Œ∫B signaling pathway to reduce vascular inflammation and apoptosis in myocardial infarction by targeting PTEN
(A) Based on STRING and Cytoscape analysis, 69... (B) The most significant module was identified... (C) Significantly enriched pathway terms of the...
(A) Leishmania spp. promastigotes... (B) Trypanosoma cruzi trypomastigo... (C) Entamoeba histolytica trophozo... (D) The Apicomplexa parasites Eime...
4‐HB = 4‐hydroxybenzoic acid; DMQ = demethoxyubiquinone or 2‐polyprenyl‐6‐methoxy‐3‐methyl‐1,4‐benzoquinone; DMeQ = 2‐polyprenyl‐5‐hydroxy‐6‐methoxy‐3‐methyl‐1,4‐benzoquinone; β‐RA = β‐resorcylic acid
Interaction between the TGF-β signaling pathway and HCV core protein
Interaction between VEGF signaling pathway and HCV core protein
Interaction between Wnt/β-catenin signaling pathway and HCV core protein
Interaction between the PPARŒ± signaling pathway and HCV core protein
Signaling pathways associated with specifically regulated genes 28 days after cAgNP exposure.Notes: Pathway Studio was used to explore the interactions among differentially expressed genes.
PG biosynthesis, receptors and signalling pathways
PG‐cytokine crosstalk in the regulation of lymphocyte‐mediated chronic inflammatory responses
Molecular mechanisms for PGE2‚Äêcytokine crosstalk in facilitation of adaptive Th1 and Th17 cell responses
A schematic view of therapeutic opportunities targeting mutp53 and the homeostatic mechanisms it coordinates in cancer cells
A proposed model of the mechanism of GALNT6-mediated regulation of proliferation and metastasis thought β-catenin /MUC1-C signaling in breast cancer
Growth and nutrient signaling pathways involve soluble signaling factors, membrane bound receptors at the cell surface, intracellular sensors, and intracellular kinases which mediate signal transduction and amplification
Overview of the metabolic pathway dysregulations in PD
Simplified metabolic pathways of acetone biosynthesis by engineered E
Schematic of the VEGF signaling pathway acting on endothelialization.Abbreviations: VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; Shc, src homology 2 domain containing; RAS, family of related proteins
Model of neuroprotective effects of DBS at the synapse
Tissue-specific gene regulatory network of the top KDs in psoriasis
Schematic representation of the central role of C1 inhibitor in various plasma systems.,  Upon contact with negatively charged surfaces factor XII (FXII) is (auto‚Äê) activated to activated factor XIIa (FXIIa)
Selective Autophagy degrades cell cycle proteins
(A) PMA activates the PKCŒ±/Erk1/Erk2/NADPH oxidase pathway to enhance R... (B) PMA activates the PKCŒ±/MAPKs/NADPH oxidase/ROS/NF-Œ∫B or PKCŒ±/Akt...
Methyltransferases linked to regulation of autophagy
Cell migration elicited by chemotactic GPCRs via the Gβγ–P-REX1–Rac pathway is mainly mediated by Gi over Gq or G13 because of the tight control that Gαq and Gα13 subunits exert on Gβγ
. A postulated scheme for the signaling pathway of arsenite-induced autophagy and apoptosis in HEK293 cells.
A schematic model of intracellular signaling mechanisms regulating proteasome inhibitor-induced apoptosis by FLT3-ITD involving the STAT5/Pim axis and the mTORC1/eIF4F/Mcl-1 pathway
Crosstalk between hepatocytes, hepatic nonparenchymal cells, and ncRNA during the pathology of NAFLD
Lysosome as the nutrient sensor and signaling hub of the cell
Effects of ketamine on the glutamatergic synapse
The extracellular parts of TLRs are activated after binding with ligands, and the conformation changes lead to convergence of downstream molecules, which triggers the signaling pathway and induced the up-regulation and activation of cytokines, chemokines, and other co-stimulatory factors
Endoglin, mutated in HHT1, is a coreceptor of ALK1 for BMP9/10 ligands, whose signaling inhibits endothelial cell proliferation and mural cell recruitment
Phosphorylated AMPK increases eNOS-mediated NO availability, that accounts for the majority of AD cardioprotective effects
A graphical representation of NLRP3 inflammasome activation in APCs by phagocytosis [] of metal implant debris, which promotes IL-1β signaling and the induction of a Th17-cell phenotype
Iron handling in the tumor microenvironment
TREM2 activation and downstream signaling
Proposed model of molecular interactions and clustering analysis
The role of kinases in the insulin signaling cascades and its interaction with nutrients in control of FOXO1-mediated physiological function
The stress signal path model of WRKY participation
Top left: Wnt binds to the Frizzled receptor (Fz) and the LRP5/6 co-receptor
Comparison of a canonical, cAMP-signaling pathway in the human host cell and in Apicomplexan parasites
Proposed model of ChemoRx-induced effects on PAF-R-dependent gemcitabine-induced MVP release
Proposed mechanisms of polycystins implication in CRC
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) mutations in the cytoplasmic region of the cysteine-X-cysteine chemokine receptor CXCR4 result in gain-of-function
Biological interaction networking of identified HCAECs phosphoproteins in KD
The ventral tegmental area (VTA)–nucleus accumbens (NAc) circuitry is regulated by a local molecular clock, which controls the transcription of genes involved in the dopamine (DA) signalling pathway, including those encoding: tyrosine hydroxylase (TH), the major rate-limiting enzyme converting tyrosine to the DA precursor l-dihydroxyphenylalanine (l-DOPA); cholecystokinin (CCK), a neuropeptide released from presynaptic DA terminals to suppress further DA release; and monoamine oxidase A (MAOA), a mitochondrial enzyme used to metabolize monoamine neurotransmitters, including DA
TGFβ1 and IGF-1 repress each other‚Äô signaling and consequent cellular response (apoptosis and survival, respectively), in bovine mammary epithelial cells
A VGF/BDNF/TrkB autoregulatory feedback loop stimulates synaptic plasticity changes in response to rapid-acting antidepressant treatment
Regulation of the oxidative arm of the pentose phosphate pathway, adapted from Jiang et al
Schematic diagram showing the apoptosis effects of MB8 in HepG2 cell
Current and future medical options for tumor control in neuroendocrine tumors
Network built up with the genes included in the endodermal carcinogenic gene signature (ECGS) derived from ToxoFunctions identified by Ingenuity Pathway Analysis (IPA) analyses
The biological parts utilised for combinatorial construction of a lycopene biosynthetic pathway
IL-37 signaling pathway induced by TLR2/4 extracellularly and intracellularly
The mechanism of Nrf2 activation and Nrf2-mediated antioxidant responses in the lungs
Summarized molecular pathway of BDNF/TrkB's oncogenic role
The domain structure of receptor-interacting protein 1 (RIPK1) consists of an N-terminal kinase domain, an intermediate domain and a C-terminal death domain (DD)
The regulated signal pathways and transcription factors of NCX1 in digestive diseases
Latency-reversing agents of the “shock and kill” approach
A schematic model showing the antiangiogenic and anti‚Äêinflammatory functions of CUR in human ESCs
The relationship between autophagy and cytokines
Visual representation of molecular interactions in the HSF flock
Visual representation of molecular interactions in the TSF flock
Mechanism of whey protein/resistance training to induce muscle protein synthesis
Comparing ECM-receptor interaction pathway for (a) DA and (b) non-DA neurons based on DEGs and DEmiR
. Model for the signalling role of O2˙– in IR cells and mice.
Schematic of proposed molecular model of non-coding RNAs involved in CXCL12/CXCR4-induced CRC invasion and progression
Schematic illustration of the possible signaling pathways induced by nsPEFs in MSCs
1Œ±,25(OH)2D3 attenuates Il-6 and IL-1β-mediated inflammatory responses in MacCM-stimulated human white preadipocytes
Representation of signaling pathways upstream of MTORC1
Schematic representation of effectors downstream of MTORC1
VEGFq binds to the VEGF promoter and stabilize the G-quadruplex structure on the opposite stand, this results in downregulation of VEGF transcription
Proteins that are only involved in the SHO1 branch are shown in light green
a | The circadian nuclear receptor REV-ERBα is maximally expressed in mice at Zeitgeber time (ZT) 10, during the light period, and is nearly absent 12 hours later in the dark period (at ZT 22)
a | Histone deacetylase 3 (HDAC3) prevents the precocious differentiation of cardiac progenitor cells and premature expression of cardiomyocyte genes–
a | Histone deacetylase 3 (HDAC3) controls brain development through maintenance of T-box brain 1 (Tbr1) gene expression or preservation of the Tbr1+ progenitor cell population
a | Histone deacetylase 3 (HDAC3) regulates the differentiation of lung epithelial cells through repression of the Dlk1-Dio3 and miR-17–92 microRNA (miRNA) clusters
Effects of social rank on blood cell gene expression and regulation vary by species and treatment according to two new studies in PNAS (, )
Relative to the control group, the red labeled protein was associated with the up-regulated gene and the white labeled protein was associated with the down-regulated gene
Proteomic and Functional Analysis Reveals an Increased Chk1 Activity in Lung Cells that Contributes to Cisplatin Resistance(A) Identification of genes involved in differential cisplatin response
Mitochondria-to-nuclear retrograde signaling pathways in mammals
Growth signal activates ATF4 and mitochondrial metabolism
Cooperative gene regulation for mitochondrial quality control by Nrf2 and ATF4
Targeting LCSCs by suppression of autophagy and Nanog.Autophagy positively regulated LCSCs by suppressing p53 and favoring the activity of Nanog
Schematic diagram of putative genes and their expression patterns in the biosynthetic pathway of astaxanthin in H
Model of ALDH1A1 regulation, potential retinoid signaling pathways, and functional effects of ALDH in CSCs
Molecular interactions in Immunometabolism governing lipid metabolic disorders
The Wnt signalling pathway uniquely identified by ce‚ÄêSubpathway
The MI‚Äêrelated subpathways where key nodes are annotated
(Top) A signaling pathway for lung cancer
Off-target resistance mechanisms generally involve activation of bypass signalling pathways (blue boxes) which could be downstream of the oncogenic driver pathway (red box) or a parallel signalling pathway that could sustain survival and proliferation of tumor cells even in the presence of the TKI
Factors contributing to variation in developmental processes include A) gene-gene interactions, B) gene-environment interactions, and C) developmental stochasticity
Protein-Protein interaction network of the 214 identified proteins: network nodes represent proteins, network edges indicate the strength of data support (STRING v10.5)
At low concentrations (≤0.2 µM) in aRMS and eRMS cells AJ-5 induces DSBs leading to increased levels of γH2AX and activation of both the canonical DSB pathway (ATM/Chk2) and the p38/MAPK stress signalling pathway.
Ovarian aging triggers miRNAs dysregulation that would impact on genes/proteins involved in the PI3K/AKT signaling pathway, thereby contributing to the depletion of the primordial follicle pool
Proposed model of PI3K activation in CM-RES clones
Schematic diagram of the molecular mechanism of ZNF326-mediated regulation of Wnt signalling
Differential gene expression involved in the KEGG pathway regulated by TRF treatment, i.e., (a) cell cycle, (b) p53 signalling pathway, (c) FoxO signalling pathway, (d) Wnt signalling pathway, and (e) ErbB signalling pathway.
Mutation enrichment of Nectin adhesion pathway
Right side: SNO of RYR lead to Ca++ release from the ER
Protein–protein interaction (PPI) network in cluster 1 from the MCODE sub-network analysis
Proposed regulatory network from Ingenuity Pathway Analysis software
Internalization and cellular trafficking of FGFRs
Functional analysis of significantly changed proteins (SCPs)
Schematic diagram on the molecular mechanism of the anti-adipogenic effect of 10-HDA in 3‚ÄâT3-L1 preadipocytes
Splenic sympathetic nerve-mediated anti-inflammatory pathway after stroke
Overview of the tumour necrosis factor receptor 1 (TNFR1) signalling pathway
VEGF secreted by tumor cells promotes neovascularization via downstream pathways including the MAPK signaling pathway, FAK pathway, PI3K/Akt pathway, and p38 MAP kinase pathway, it also directly promotes tumor cell proliferation
Proposed mechanism of how solid stress signal transduction via Akt pathway regulates GDF15 expression to induce pancreatic cancer cell migration
Silencing of cyclinB1 elevated the reactive oxygen species levels
(A) Wnt-off. In the absence of Wnt stimulation, β-catenin is phosphoryla... (B) Wnt-on. Upon Wnt stimulation, the destruction complex is not functio...
The molecular mechanism of S1P signaling via its receptors
Overview of the role of the biomarkers explored in the study on EGFR signaling
. Revised biosynthetic pathway for dihydrobenzo(ghi)perylenequinone 1 and cyclohepta(ghi)perylenequinones 6 and 12.
New targeted therapies in advanced primary cutaneous anaplastic large cell lymphoma
Model describing the distinct fates of NK cells during NK cell education
An integrative schematic view of the human and plant terminal telomeric complex
Proposed scheme of the antitumor effects of DIFs
Proposed scheme for the glucose uptake-promoting effect of DIFs
Transfection with GAB increases the sensitivity of GBM cell lines T98G, U87MG, and LN229 to H2O2-induced oxidative stress
FoxO functions in cell response to antitumor drugs
TRPML1-3 and TPC1-2 in the endocytic pathway
Filovirus replication cycle showing host and viral proteins that either promote (green boxes) or block (red boxes) virion assembly and release
Differential expression of genes in the IPA canonical pathway “GPCR-Mediated Integration of Enteroendocrine Signaling Exemplified by an L Cell.” Genes with significantly lower expression in domesticated turkeys relative to Eastern wild birds after AFB1 treatment are denoted in green
A schematic diagram of CB2R mediated signaling
Schematic diagram of the molecular function of KRT19 as a regulator of cancer properties through differential modulation of the Wnt/β-catenin/Notch signaling pathway in colon and breast cancers
Schema of miR-451 regulated YWHAZ pathway
Schema of miR-19a-3p regulated Fra-1 gene pathway
Proposed model by which polyphenols may modulate oxidative stress-induced pathways including Ang II, VEGF and TNFŒ±
Selected enriched KEGG pathways among DETs between S41 and S43 during tail resorption
The intracellular signaling pathways induced by Theiler‚Äôs murine encephalomyelitis virus: Detection of dsRNA by TLR3 and ssRNA by TLR7 in endosomes leads to the recruitment of TRIF and MyD88, which interact with TRAF3 and TRAF6 to trigger MAPK, NF-Œ∫B, and IRF signaling
Alterations of the PI3K/Akt-Cyclin D1 pathway in cell cycle progression from G1 to S phase in 2-cell embryos
PI3K pathway inhibitors target one or more aspects of PI3K signaling
Graphical model of IL-1β activation of signaling pathways leading to acquisition of resistance to cisplatin in breast cancer cells
Model of estrogen signaling pathways in cancer
Schematic diagram of apoptosis induced by Endoplasmic Reticulum (ER) stress
Cartoon representing the osteolytic and osteosclerotic vicious cycles
The hepatic metabolism of lipid and carbohydrate through insulin induced transcriptional regulation and circadian clock
A suggested model of brassinosteroid (BR) regulation of immunity at multiple levels
Oxygen- and hydroxylase-dependent mechanisms regulating hypoxia-inducible factor 1 (HIF-1) activity
HIF-1-dependent reprogramming of the glucose metabolic pathway, and resultant radioresistance
The putative pathway and analysis schematic diagram of glucose repression in K
UVB-induced ROS production followed by the activation of both JNK and p38 MAPK subfamilies, leading to apoptosis and photoaging on fibroblasts (red arrows)
Schematic of the mechanism of miR-34 in EMT
Molecular signaling of inflammatory pathways involved in structural remodeling
COLLV defect is associated with pathological ECM remodeling and anoikis, which is rescued by an Œ±vβ3 integrin-EGFR signaling transduction pathway [], together with defective ER homeostasis, autophagy and cell cycle progression
Smad3 linker phosphorylation negatively regulates transforming growth factor‐β (TGF‐β)/Smad3 signaling
Schematic diagram of the different types of GSLs
Cerebellum (CB)-specific biological processes in Alzheimer’s disease (AD) brain
Schematic of activated TLR4 signal inhibited by neurosteroids
The three branches of the unfolded protein response (UPR)
Metabolic engineering strategies for enhancing citric acid production
Overview of SiNPs-induced apoptotic and necrotic cell death pathways independently in HUVECs
Associative gene network describing interactions between three central genes/proteins of the extrinsic apoptotic signaling pathway biological process
Multiple nonunidirectional levels through which autophagy-related processes in senescence affect regulation of SASP genes, often via NFkB activation
A simplified diagram of the model showing upregulation of MMP13 by pro-inflammatory cytokines, the protective effect of the TGFβ/Alk5/Smad2/3 pathway and the detrimental effect of TGFβ/Alk1/Smad1/5/8 pathway
The complex interplay between CCT and actin and tubulin
Pathways to DHT synthesis (modified from Ref
The FGFR1 pathway promotes NF-Œ∫B signaling
A proposed model of intracellular pathways engaged within, and functions of, HSV-specific CD8+ T cells from protected ASYMP individuals
Pathways affected by the combined selected kinase inhibitors in BRAF mutant melanoma cells
Pharmacology of rapid-acting antidepressants in corticomesolimbic brain circuits
A) Experimental design depicting the sampling time points represented as... B) Schematic representation of the retinoic acid signaling pathway. Gene...
Chronic hyperglycemia impairs neuron function
Schematic representation showing phagosomal rupture-mediated phagosomal escape of MAB-R in infected murine macrophage, leading to Type I INF production via the cGAS-STING-IRF3 axis
IPKB analysis of relationships among upregulated genes on silk film topography
CXCL16/CXCR6 interaction promotes endometrial decidualization via PI3K-PDK1-AKT-Cyclin D1 pathway
miRNA-223 may be an anticancer gene in NSCLC through the PI3K/AKT pathway by targeting EGFR
Proposed model of AKAP13 and PR-B signaling in fibroids
B-cell receptor pathway, which may be dysregulated in TNBC
MAPK signaling pathway, which may be dysregulated in TNBC
mTOR signaling pathway, which may be dysregulated in TNBC
The pathway involved in gemcitabine-resistant pancreatic cancer cells with digoxin treatment
Euglena gracilis has flexible and fault-tolerant mitochondrial metabolism
The central role of T lymphocytes in acquired immunity
Differences between glycolysis and the tricarboxylic acid cycle
Different signaling pathways are activated by different stimuli
The role of mtDNA in activating the innate immune response
Bt-resistance mechanisms in target pests
The roles of circRNAs in cancer phenotypes and biological characteristics (proliferation, migration, invasion, and angiogenesis)
Schematic and simplified representation of the several components of the IGF-1/PI3K/AKT/mTOR pathway discussed in this review
FGFRs signaling pathway could be elicited by FGFs with the existence of heparin
The figure illustrates the signal transduction cascades of TGF/BMP, Wnt, Hedgehog signaling pathway in the development of cranial sutures
A schematic illustration of the proposed model depicting a p53/miR-27a/NFAT5 mediated regulatory pathway in mouse GCs
Schematic map describing apoptosis induction of the TRAIL and Andro combination therapy
NLRP3 inflammasome pathways and putative mechanism by which cyclic stretch negatively regulates IL-1β secretion in murine macrophages
Proposed mechanisms of action of glutamatergic modulators and other putative rapid-acting antidepressants
At the maternal-fetal interface, DSC-derived RANKL enhances the accumulation of dγδ T cells by upregulating cell-adhesion molecule expression on DSCs and γδ T cells, and promotes the polarization of dγδ T cells into Foxp3+regulatory cells possibly by activating NF-κB pathway and inducing TGF-β1 production in early pregnancy
The pink and green nodes represent the important genes identified by previous analysis and the transcription factors that have regulatory relationships, respectively
The proposed divergent role of Notch signaling in endothelial and smooth muscle cells
Schematic representation of Nrf2 signaling in homeostasis and a deregulated environment
Schematic diagram of the regulatory role of GRK2 in TLRs-mediated signaling pathways for iNOS expression in microglial cells
The potential proinflammatory role of resistin in the pathogenesis of osteoarthritis
Molecular mechanisms for renoprotection of EGCG
Aberrant protein conformations are a major cause of ER disease
Signal transduction pathway related to the immune-regulation of botanical polysaccharides in macrophage activation
Potential explanations of impaired effect of tolerogenic DCs in vaccine generated from patients with chronic hyperglycemia
Pathway map of Notch signaling (A) and Th1 differentiation (B) in KEGG
Speculated antioxidant related signaling pathways induced by APS in MEFs
Schematic of mechanistic cross-connection between the transforming growth factor beta pathway and bone morphogenetic protein signaling
The Cek1 and Mkc1 MAP kinase cascades, and their respective upstream activator signaling proteins are shown
In the cytosol, CRTC1 is phosphorylated at S151 by the cAMP-SIK pathway and is inactivated through interactions with 14–3–3 proteins
PAK4 is activated downstream of PKA in the α-MSH signaling pathway and activates the CREB–MITF pathway
Frequent genetic alterations in genes from angiogenesis pathway in UBC
Proposed model of IFN and inflammasome activation by HCMV and IL-1β inhibition by IE86
Insulin resistance mechanism and potential sites of vanadium activity
Potential neuroprotective mechanisms of antidiabetic drugs in the context of Parkinson’s disease dementia
Schematic representation of the interactions involved in the alteration of DC function following exposure to F
The IFN-Œ± is cleared via the binding to the respective receptors in the liver
Mechanisms of MDSC-dependent promotion of PMN formation and evolution
Schematic overview of DNA demethylation during glioma progression
Schematic relationships between the wound-induced signal transduction mechanisms for the sesquiterpene biosynthesis and regulation in Aquilaria species for the agarwood production
Different forms of programmed cell death and associated cascades
The canonical pathway has potential Δ4 and Δ5 subpathways
Predicted pathways for regulating rice drought memory response
Mutations in key pathways controlling cell growth
Schematic representation of the pathogen‚Äêderived molecules employed to evade the intracellular DNA sensing pathway
Schematic diagram illustrating insulin-induced PD-L1 up-regulation and EGF help in PD-L1 transport in colon CSCs
The GPL pathway constructed in this study
Cell death pathways currently implicated in motor neuron cell death in ALS and related miRNAs
WWOX controls TGF-β, Hyal-2, and Wnt signaling pathways that cross talks with the Hippo signaling
Strategies to overcome NK resistance in solid tumors
The Life Cycle of AAV Vectors and the Basis of the Development of Tyrosine-, Serine/Threonine-, and Lysine-Modified Next Generation of Recombinant AAV Vectors(A) Following AAV2 binding to its primary cell surface receptor, heparan sulfate proteoglycan (HSPG), the vector interacts with human fibroblast growth factor receptor 1 (FGFR1) as one of the co-receptors to gain entry into cells via a Clathrin-coated pit, traffics through early and late endosomes and becomes phosphorylated by epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK)
Intracellular hyperglycemia results in increased production of mitochondrial ROS
PLK-dependent latent TGF-β activation and TGF-β/Smad signaling pathways
Cholinergic signaling via nAChRs and muscarinic acetylcholine receptors (mAChRs) regulates striatal function
Rationale for choosing Arl13b, SMO, and melanin-concentrating hormone receptor 1 (MCHR1) as cilia-targeting moieties
The regulatory mechanism of LA1 on the activation of TLR4 pathway
Model hypothesizing the potential regulation of β-catenin by G-alpha subunits and PMT
The overview of PI3K/AKT/mTOR signaling pathway
Targeting PI3K/Akt/mTOR pathway in cancer
The schematic diagram shows the mechanism underlying cTFRC as a ceRNA for miR-107
IL-17 inhibited fungal keratitis by reducing the level of CX43 through the AKT signaling pathway
A simplified representation of the Hedgehog (Hh) signaling pathway and its role in basal cell carcinoma (BCC) pathogenesis
Schematic representation of canonical and non-canonical NF-Œ∫B pathway
A proposed regulatory mechanism of the Fbw7-XBP1s axis pathway
Signaling pathway analysis for Amphetamine, a stimulant with addiction
Signaling pathway analysis for Theophylline, an antagonist of adenosine A2a receptor for drug abuse
Hypothetical mechanisms of the intracellular pathways underlying the results found in this study
Proposed mechanisms of obesity-induced BAT depletion
Schematic of GPCR/EGFR-CARMA3 signaling pathway leading to NF-Œ∫B activation
An illustrated view of Netrin-UNC5B signaling
Schematic representation of deregulated Wnt signaling pathways in the BM of ENU induced experimental leukemic mice
Modified KEGG map of the JNK and p38 MAP kinase signaling pathway showing transcriptional changes
Anti-metastasis effect of inotilone and the proposed signaling pathway
In this mechanism, during the osteogenic differentiation, the depletion of miR-185 upregulated Bgn expression, so as to activate the BMP/Smad1/5/8 signaling
ZINC24469384 regulates genes involved in P53 and STAT signaling pathways
Schematic representation of NO signaling mediating NMDA-R activation in the central nucleus of the IC
Roles of PARPs in the immune response after pathogen invasion
Model of Nucleotide-binding oligomerization domain-containing protein (NOD)1 and NOD2 signaling cascades
Model of cofilin regulating the actin cytoskeleton and initiating PHEV entry
There are two pathways underlying glutamate toxicity mechanism integrated in parallel in neurons; receptor-mediated excitotoxicity pathway and nonreceptor-mediated oxidative stress pathway
Signaling pathways interconnecting V-ATPase and glycolysis
V-ATPase integrates glycolytic signals to control cellular metabolism
Suppositional pathway of AT together with PS-induced apoptosis in HepG2 cells
The NOD1 and TLR4 signaling pathways and the main target of CBN in the suppression of LPS-induced inflammation
Axin/TNKS binding contributes to the nuclear translocation of β-catenin and the further activation of the WNT pathway in Amot-p130 negative cells (left)
CXCL5 increases AKT phosphorylation in a CXCR2-dependent manner and then NF-Œ∫B translocates to the nucleus
Networks representing protein-protein interactions in differentially regulated proteins from the NOD1 (HS578T/NOD1) (a) and NOD2 (HS578T/NOD2) (b) experimental groups
Yin-Yang model of hair follicle regeneration tuned by Wnt/BMP signaling
The homologous recombination (HR) repair deficiency represents an opportunity for a synthetic lethality approach through the use of PARP inhibitors (PARPi)
LINC00968 was lowly expressed, whereas WNT2 was highly expressed in breast cancer tissues and cells
miR-506 inhibited the expression of LHX2, which hampered TCF4 expression and inactivated the Wnt/β-catenin signaling pathway, consequently inhibiting tumor growth and metastasis in NPC
Schematic illustration of the AMPK/mTOR signaling pathway in TNBC tumor growth and progression
Molecular pathways of cellular senescence
The presence of extracellular arginine enhances arginine uptake by binding to the SPS-sensor, leading to the endoproteolytic activation of transcription factor Stp2
Immune pathways highlighting differential expression of genes following exposure to Rlow and LAVs
Differences in the functional impact of IL-7/IL-7R-mediated signaling in T-ALL cells and their normal counterparts
The signaling transduction of mTOR pathway
(A) Visualization of metabolic dynamics of primary metabolism in skin ti... (B) Partial of representative metabolites. The relative levels of metabo...
Energy metabolism and lactate shuttling between astrocytes and neurons
cAMP regulates immune response of astrocytes
Mechanism of suppression of FN-induced EMT by cirsiliol in B16F10 metastatic melanoma cells
Proposed mechanism of EtOAc extract of L
Model for THD on a crosstalk in Fzd/GSK3β/β-catenin/P62 axis
Schematic illustration of myostatin signaling pathway in sarcopenia
The representative cardiovascular disease pathway
The representative liver disease pathway
The mammalian or mechanistic target of rapamycin (mTOR) complexes and signaling pathway of mTORC1 and mTORC2
Schematic depiction of the mTOR signaling network
Short- and long-term action of ceramides on insulin signaling in muscle cells
Potential for using mTOR in PD treatment
Schematic overview of the autophagy process and genetic and drug targets to inhibit specific aspects of autophagy
The pathways controlling the response of physioxia MSC chondrogenesis
One proposed mechanism for how vascular endothelial growth factor/neuropilin (VEGF/NRP) signaling impacts cancer stem cell (CSC) function independently of VEGFRs
Activation of signaling pathways in respiratory epithelial cells upon viral infection
Model of the association between bacterial translocation hypothesis and related traits of Crohn’s disease in the pathophysiology of chronic fatigue syndrome
A representative pathway featuring multiple enzyme-/non-enzyme-assisted post-translational modifications (PTMs) that control cell-decision making
IPA to identify the signaling pathway associated with the differentially expressed proteins across all the conditions studied
TRPV1 activates a complicated pathway that converges on NR1 trafficking in remifentanil-induced postoperative hyperalgesia.Notes: Schematic illustration of proposed TRPV1-CaMKII/PKC-NR1 signaling in remifentanil-induced postoperative hyperalgesia
Schematic diagram of intrinsic and extrinsic pathways of neutrophil apoptosis
Comparative analysis of genes in regeneration-related signaling pathways of regenerative animals
Modules of core PPI networks of baicalein against HCC
De novo biosynthesis of various aromatic compounds derived from the SHK and aromatic amino acid biosynthesis pathway
The metabolic engineering approaches to microbial production of SHK pathway derivatives
The metabolic engineering approaches to microbial production of aromatic amino acid derivatives
The schematic representation of TLR and JAK-STAT pathways postulated in the slug I
Schematic overview depicting regulatory pathways for PYY and GLP-1 secretion by enteroendocrine L-cell
Model of GPCR/β-arr-dependent signal pathways controlling cell survival, cytoskeleton remodeling, and gene expression, leading to enhanced cell growth, invasion and metastasis
Structural simplicity of the JAK–STAT signalling pathwayAfter the engagement of cytokine receptors constitutively bound to JAK, JAK is activated and in turn phosphorylates the cytokine receptors, resulting in phosphorylation of STAT, which subsequently translocate into the nucleus, where it regulates gene expression
Model of anchorage-dependent regulation of cell survival and glucose metabolism
Graphic image representation of the possible mechanisms of lung inflammation in COPD involving purinergic signaling pathway
PI3K/AKT/mTOR and ERK signalling pathways associated with cardiac hypertrophy
Notch signaling pathway as seen in the KEGG database (hsa:04330)
Levels of regulation of NKG2DL expression
Illustration of most of the proposed modes of action of antitumoral POMs
A working model of how HCV-mediated inflammation is propagated by HCV core protein in macrophages
Protein kinase C pathway for prolactin regulation of metabolic gene expression in prostate epithelial cells as represented by mitochondrial aspartate aminotransferase
Activated STAT3/5 signaling pathway by IL-6 receptor, Prolactin (PRL) receptor, VEGF Receptor, EGF Receptor, and IL-10 receptor
RAS induces the proliferation and migration of cancer cells via NOX1
Activation of NADPH oxidase NOX2 assembly
SOD2 and SOD3 in cell metastasis and in cell survival
Glycolysis pathway showing how increased PFK-2/FBPase-2 expression and phosphorylation, stimulates glycolysis via increased fructose-2,6-bisphosphate synthesis acting as a powerful allosteric activator of PFK-1
During AVC development, oscillatory flow activates mechanosensitive calcium channels Trpp2 and Trpv4 in the endocardium, which then promote klf2a expression ()
Schematic map of the potential signaling pathway showing alleviation of neuronal apoptosis by NaB via DJ-1/Akt-related anti-oxidative stress pathway
Transcription factor regulatory effect network identified using Ingenuity Pathway Analysis (IPA)
Biosynthetic pathway of core M1, core M2, and core M3 O-Man glycans in the ER and Golgi
Hedgehog signaling and Wnt signaling in the primary cilium
Upon stimulation with DNA or by viral infection, the pattern recognition receptor (PRR) cGAS produces the second messenger 2′3′‐cGAMP, which binds to the ER‐resident protein STING
Protein–protein interaction networks.Notes: Upexpression genes were analyzed and constructed a network
The hypothesized mechanism of DS on learning and memory
Promoter hypomethylation of genes involved in myogenesis, structural dynamics of muscles and CDC42 signaling
Proposed model of cell signaling associated with the ALK5-SMAD2/3 tumor-suppressive arm identified by Monsivais et al
AhR‚àíAREG axis defines a signaling pathway between cellular intrinsic redox mechanisms and surrounding TME
The critical roles of β3GalT5 and the globo-series GSLs in regulating the apoptosis and survival of breast carcinoma cells
Poly(I:C)-toll-like receptor 3 signaling pathway and polarization of mesenchymal stem cells
A schematic representation of GnIH action at the hypothalamic-pituitary levels
Schematic of the insulin-like growth factor system role in PMSC differentiation into the skeletal muscle
Proposed mechanism by which type 2 diabetes (T2DM) and aerobic exercise can affect the brain and lead to alterations of hippocampal glucose metabolism with subsequent effects on synaptic plasticity-associated proteins
Key components and potential pharmacological targets of Wnt signaling implicated in orofacial clefts
Crosstalk between Wnt, Cdh1, Bmp, Tgfβ and Fgf signaling pathways in orofacial clefts
Crosstalk between Wnt, Shh, primary cilia and other related signaling components in orofacial clefts
Crosstalk between Wnt, RA and related signaling pathways in orofacial clefts
The control of aerobic glycolysis by ERK and JNK signaling pathways in proliferating cells
ERK- and JNK-mediated phosphorylation of PKM2 is at the crossroad between proliferation and apoptosis
Regulation mechanism of ECM/integrin/EphA1‚Äêmediated cell adhesion
Schematic models of molecular targets affected by ISE to attenuate inflammatory signaling pathways
Disorders resulting from mutational defects in the SL synthesis pathway for ceramide and GSLs and the nonlysosomal SL degradation pathway
Disorders resulting from mutational defects in the lysosomal SL degradation pathway
KIT mutant GISTs have enrichment for KEGG cell cycle pathway (p = 0.0007) and spliceosome pathway (p = 0.0008) using STRING v10 clustering of significantly somatic mutated genes (p < 0.003)
PTP1B modulates IL-8 production via a SFK-Akt-GSK-3-C/EBPß pathway
Mapman pathway overview of cellular response and stress pathway of modules up-regulated under heat stress (M1 and M2) and modules down-regulated under heat stress (M3–M5)
Regulation of the C-type lectin receptor signalling pathway by curdlan and MacroGard®
Mechanisms of cell damage in peripheral neurons caused by cigarette smoking
Pathogen antioxidant networks: The examples of Mtb and T
Models for the roles of Scribble in organizing molecular interactomes involved in synaptogenesis, epithelial polarity, and adhesion, and growth regulation
TGF-β; tumor growth factor-beta, ŒúAPK/ERK; Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell, PI3K/AKT; PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle
Effects of EBV latent and lytic proteins on inhibition of apoptosis
Notch pathway promotes drug resistance by regulating cancer cell survival, glycolytic switch and cancer stem cells
The kynurenine pathway with a focus on KYNA synthesis
PIN1 acts at multiple levels of cooperating cellular pathways
Schematic representation of AMF secretion and interaction with GPER-1, which drive EC progression
a Sugar metabolism pathway components and corresponding heat-map expression profiles of sugar-related genes in 6-BA treated buds of ‘Nagafu No.2’ apple
Possible intracellular and extracellular functions of FABP4FABP4 is abundant in the cytosolic fraction of adipocytes and can bind one long-chain fatty acid (FA), including palmitic acid (PA), stearic acid (SA), oleic acid (OA), linoleic acid (LA) or Œ±-linolenic acid (ALA)
The biogenesis of mature, secreted clusterin involves the traditional secretory pathway common to other secreted proteins
Functional mechanisms of COL2A1 on the BMP-SMAD1 pathway
Schematic showing the role of the Wnt/Frizzled signaling pathway and potential mechanisms of the neuroprotective effect on early brain injury.Briefly, the Wnt/Frizzled signaling pathway is suppressed after SAH, which is accompanied by markedly decreasing Wnt1 protein secretion and expression
Modulation of autophagy the signaling pathway by electroacupuncture (EA) for treating cerebral ischemia/reperfusion (CIR) injury.EA activates class-I phosphatidylinositol 3-kinase (PI3K) to promote the generation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), which can activate protein kinase B (AKT) through phosphorylating AKT at Thr308 and Ser473
TGFβ mediated EMT drives the transcription factors SNAIL1 and TWIST to induce the first layer of the core regulatory network
Network modeling of the epithelial-to-mesenchymal transition (EMT)
Major pathways converging on uncontrolled growth in Drosophila epithelial cells
IIP-effectors in FOXJ1 regulatory network and their probable ciliary associations
Schematics shown miRNAs which might regulate mGluR/mTOR/LTD signaling
Regulation of B cell receptor (BCR) signaling on B cell survival
Scheme summarizing the role of TRP channels in cardiac fibrosis
Summary of the role of TTC7A in intestinal epithelial cells and the consequences of its mutation
miR-155 role in increased ROS production: miR-155 increases ROS production by silencing SOCS, a negative regulator of the JAK/STAT signaling pathway, a pathway known to play a role in ROS generation
Consequences of indoleamine 2,3 dioxygenase (IDO) overexpression on the antitumoral immune response
Network analysis of differentially expressed genes
Scheme of proposed IS-induced apoptosis via ROS-NRF2 and MAPK signaling pathways in human astrocytes
Protein–protein interaction network of associated genes in the etiopathogenesis of ANCA-associated vasculitis
TNF-related apoptosis-inducing ligand (TRAIL)-induced signaling pathways
Schematic representation of major calcium channels, pumps, exchangers and sensors in mammalian cells
Differentiated insulin-producing cells (IPCs) for transplantation
—Visualization of the p53-signaling network modified from the KEGG pathway
MCSP- and ABCB5-enriched CTCs exhibit distinct transcriptional programming, with ABCB5 CTCs displaying an invasive phenotype
Mammalian target of rapamycin (mTOR) pathway
Schematic diagram of the hedgehog (Hh) pathway
MST1 acts as a regulator of the extrinsic apoptotic pathway in Jurkat T cells
Kinetochore PP2A-B56 and PP1 promote the stability of microtubule attachments and efficient Spindle Assembly Checkpoint silencing in animal cells
Proposed pathway explaining some biochemical effects, induced in vitro by PBDEs, on cell cycle, antioxidant status, metabolism and proliferation
LRRFIP1/GCF2 binds to exogenous and endogenous nucleic acids and activates type 1 interferon and pro-inflammatory cytokine responses
Structural hotspots and signaling pathways that are essential to the hepatic phenotype of highly differentiated HepaRG cells
Schematic representation of cell death pathways induced by gef/apoptin
Diagram of the phosphatidylinositol 3 kinase/Akt/mammalian target of the rapamycin (PI3K/Akt/mTOR) pathway and cell cycle and autophagy dysregulation in cancer and Alzheimer’s disease (AD)
Role of Itch in Type I non-canonical Hh pathway
Proposed model for MAPK inhibition in paired TP53WT and TP53MUT cell lines selected for resistance to MDM2 inhibitors
Nongenomic and Genomic actions of Thyroid hormone and thyroid hormone receptor
Proposed mechanism of protection for oral SUB+IV vaccine against tick infestations in cattle
The proposed mechanism of LAMB3-mediated tumor antiapoptotic signaling, invasion and metastasis through the PI3K/Akt axis in patients with pancreatic ductal adenocarcinoma (PDAC)
Liraglutide increases miR-26a-5p to reduce PTEN thus increasing the levels of PIP3 to stimulate the PI3K-activated signaling cascades
Clinical Relevance of miR-582-3p and miR-582-5p with SMAD2, SMAD4, TGFBRI, and TGFBRII in Human PCa Tissues(A) Analysis of miR-582-3p and miR-582-5p expression with SMAD2, SMAD4, TGFBRI, and TGFBRII in four bone metastatic PCa tissues (T1–4) and four non-bone metastatic PCa tissues (T5–8)
rLj-112 was internalized with EGFR to suppress the downstream signaling pathways to initiate the anti-tumor steps in B16 cells
Models of replication-coupled ICL repair
Pathways impacted by SAHA in (A) MCF-7 and (B) LNCaP cells, illustrating the pathways activated by SAHA in MCF-7 cells leading to cell death, and the cycle arrest and apoptosis pathway triggered by MDM2 inhibitor (RG7388) and HDACi (SAHA) in LNCaP cells, respectively
Pathway analysis for PRR and IFN signaling
Schematic diagram showing the protective mechanism of DPHC on PM2.5-induced skin damage
Microbial-based production of nutraceuticals from simple carbon sources
Model of signal transduction pathways that mediate migration induced by OA in breast cancer cells
Model describing regulation of primary cilia length by the FGF–ICK pathway
Metabolic reprogramming of T cells after allogeneic stem cell transplantation
Schematic diagram of (A) construction of mutant E. coli strain BL21 (DE3) ‚àÜxylAB, p21XR and (B) its plausible metabolic pathway for xylitol production from xylose-based hydrolysate.
The regulation of the expression and cleavage of sterol regulatory element-binding protein-1c (SREBP-1c) and the transcriptional activation of the acyl-CoA:glycerol-sn-3-phosphate acyltransferase1 (GPAT1) gene
De novo synthesis of NAD(P) from tryptophan, nicotinamide and nicotinic acid
The proposed mechanisms model of Activin B on mouse vibrissae growth
Schematic illustration of the proposed mechanisms for the inhibitory effects of MS-275 on osteogenesis in VICs
After the skin was injured to form a wound, the alarm signal has bound and activated the NLRP3 inflammasome by damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs)
The biochemical process networks of the differentially expressed proteins generated by MetaCore™ software using a transcription regulation algorithm
Negative regulation between FoxO3a and EPS8 in EGF/PI3K/Akt pathway
Complement dysregulation in complement-mediated HUS Complement activation initiated by any of the three pathways (classical, alternative, or lectin pathway) leads to C3 activation and C3 convertase formation on C3-opsonized surfaces
Proposed mechanism of DMAMCL-mediated cell death in human glioma cells.Abbreviations: DMAMCL, dimethylaminomicheliolide; ROS, reactive oxygen species
Synthesis pathway of cardiolipin from lysophosphatidylcholine and lysophosphatidic acid
Schematic of the mechanism by which ASIC1a attenuates the activation of autophagy via elevated intracellular calcium levels and the CaMKKβ/AMPK/mTOR signaling pathway
ceRNA regulatory network associated with the MAPK signaling pathway
The dynamic mechanism of ADP-ribosylation reversal
Schematic of pathways associated with long-term potentiation in the pre-and post-synaptic membrane
The activation of antiviral pathways in Atlantic cod
Effects of statins on several pathways involved in bone metabolism
Pyruvate and glutamate are 2 major metabolic hubs in GSCs
Most important upstream signaling in the regulation of autophagy and apoptosis processes.Notes: Growth factors and nutrients stimulate the PI3K and Ras pathways, and their downstream effectors, such as Akt and Erk kinases, directly inactivate TSC1/2 complex by its phosphorylation and in this way activate mTORC1, which negatively regulates autophagy through inhibitory phosphorylation of Ulk1 and Ulk2 kinases
The reaction-based specification of the model according to the notation previously introduced
Simplified overview of one-carbon metabolism pathway
Main aspects of folate receptor signaling and C1 metabolism discussed during the meeting
Architecture of the Fanconi anemia (FA) core complex, with FAAPs (Fanconi anemia–associated proteins) indicated by numbers
Roles of FA proteins in replication stress
Illustration of FGF1 signaling in Leydig cell development
(A) The wild-type CARD9 protein consists of an N-terminal caspase activa... (B) Fungi are sensed by myeloid cells through Dectin-1, which is phospho...
Model for nobiletin inhibiting proliferation and inducing apoptosis
β-Thujaplicin treatment increased the reactive oxygen species (ROS) generation, which subsequently led to inhibition of the Akt-mTOR signaling pathway and activation of p38/ERK MAPK signaling pathway
Differences established during gastrulation through the EMT and MET processes
Regulatory loop among Kaiso, Wnt11/5a and Suz12
Schematic of protein associations and potential functions of SHARPIN in human megakaryocytes and platelets
hBM-MSCs-Ex treatment alleviates liver fibrosis in both HSCs and liver fibrosis tissues through inhibition of Wnt/β-catenin signaling (PPARγ, Wnt3a, Wnt10b, β-catenin) and the downregulation of downstream gene expression (WISP1, Cyclin D1)
EP receptors and their downstream signaling: PGE2 binds to its cognate receptors, the E-series of prostaglandin receptors (EP1–EP4) on the plasma membrane and nuclear membrane
Combating inflammation promoted by KSHV infection: KSHV infection promotes pro-inflammatory lipid mediators of arachidonic acid pathway and the enzymes involved in their synthesis
Pathway scheme with marked involved proteins
Key components of the Hippo pathway in Drosophila and mammals
GRP78 mediates hypoxia-induced EMT through smad2/3 and SRC/MAPK signaling
Pathview graph for the Kyoto Encyclopedia of Genes and Genomes term ‘calcium signaling pathway’ allows the visualization of the differentially expressed genes involved in this signaling pathway
Schematic diagram illustrating the calcium signaling pathway involved in ketamine-mediated dysregulation of UBSM contraction
Regulation of immune EP expression by Tumour necrosis factor (TNF) signalling after exposure of IPEC-J2 cells to micro algae extracts in the absence and presence of ETEC
Promoting immune evasion by Hippo pathway
Arenaviral proteins (NP and Z) inhibit the RIG-I/MDA5 and NF-Œ∫B pathways
Neurotrophic factors and their receptors in dopamine neurons
Schematic diagram depicting proposed mechanisms responsible for aniline inducedspleen toxicity
The functional enrichment and gene network analysis
Pericytes contribute in homeostasis of the BBB through different mechanisms
Under pathologic circumstances, pericytes present stemness or trans-differentiation potential
Models for potential interaction between Toll-like receptor 4 (TLR4) and protease-activated receptor 2 (PAR2)
Cytosolic glucose enters glycolysis and pentose phosphate pathways
(A) the modulation of the death receptor signalling pathway by LPS+anti-IL10 antibody and (B) the modulation of the PI3K/AKT signalling pathway by LPS+anti-IL10R antibody
The Mec1/Rad53 pathway senses ongoing DNA replication to inhibit mitotic entry
TLR2/IFN-λ3 protein-protein interaction was performed by using String software
Schematic depiction of the major pathways involved in signaling through the ALK-MYCN axis in neuroblastoma (NB)
A proposed model for role of MARK4 in regulating lipogenesis in pig placental trophoblast cells
Tangeretin-induced apoptotic pathway in BFTC-905 bladder cancer cells
Comprehensive pathway of Alzheimer’s disease derived from the Kyoto Encyclopedia of Genes and Genomes (KEGG)
The JAK2-STAT5-SOCS pathway and domain structure of STAT5
The effects of polyphenols on signaling pathways in prostate cancer
Apoptosis can be modulated by the activity of polyphenols in prostate cancer
Schematic representation of the major mechanisms involved in the response of the Vitis flower to a cold night
mTORC1 as a key hub transducing the metabolic effects of glucose and fructose in the liver
Ligand-independent and ligand-dependent transactivation of epidermal growth factor receptor (EGFR)/MAPK3/1 pathway in pig cumulus cells by FSH
The network of the cellular thiol redox system in multicellular eukaryotes
A schematic diagram for anti-ethanol caused damage in K
A brief summary of reciprocal regulation between AMPK and mTOR pathways
AMPK-mTOR signaling pathways during Mtb infection
Regulation of immunometabolism in macrophages infected with Mtb
Schematic diagram to illustrate the activation of the nuclear factor-Œ∫B (NF-Œ∫B) pathway in the radiation-induced rescue effect (RIRE)
Proposed mechanism of HoxA10-mediated inhibition of HBV replication
Sub-network of the innate signaling pathway obtained after IPA analysis of the differentially expressed genes in A549 lung epithelial cells infected with WM 06.482 conidia
Red indicates significantly up-regulated genes, green indicates significantly down-regulated genes, and blue indicates genes that were both up- and down-regulated
EA ameliorates osteoclastogenesis by inhibiting NF-Œ∫B
A schematic graph of the proposed cardioprotective mechanism of H2 when rats were exposed to CIH
Integrative pathway enrichment analysis showing the interaction between predicted and experimental targets
RANKL-RANK signaling pathway via Btk in osteoclast differentiationTec family kinases are activated by RANK and bind to scaffolding proteins (BLNK or SLP76) activated by ITAM signaling, thereby forming a complex that cooperates to activate PLCγ2
. The diverse regulatory mechanisms of lncRNAs on the Wnt signaling pathway.
Common alterations in fluorosis‚Äêproliferation and differentiation
Common alterations in fluorosis‚Äêhomeostasis & autophagy
Illustration of the FGF16 signalling pathway to regulate Leydig cell development
The model of JS‐K‐induced anti‐tumour activity in gastric cancer
The molecular process of DNA damage repair associated with PARP inhibitor sensitivity and resistance
Mechanism of Action of FSH on Adipocytes
Model for p53-HSF1-PGC1Œ± integrated responses in HD
The role of phosphodiesterases (PDEs) in the pituitary gland: After stimulation of somatotroph cells via GHRH, the G protein coupled receptor is activated, which causes a conformational change of the receptor
Influence of non-oncogenic viruses on the components of non-canonical NF-Œ∫B signaling
The schematic diagram shows the regulatory non-coding RNAs in NAFLD disease development and progression
Regulation of PD-L1 expression in response to DNA damage in cancer cells
Repair pathways and signaling in response to DSB induction by IR
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of T cell receptor signaling pathway in asthma
Complement activation pathways and examples of complement-targeting therapeutics for IgAN
Sub-pathways identified using the sub-pathway strategy
ERK signaling pathway was hyperactivated in the patient’s tumor tissue
Interesting putative mechanisms are identified by iPathwayGuide (www.advaitabio.com) on the Glutamatergic synapse and the Chemokine signaling pathways
The neuroprotective effects of osteocalcin (OCN) in rats with Parkinson’s disease (PD)
The possible therapeutic implications of resveratrol/metformin/exercise in cognition through osteocalcin signalling
Schematic representation of complement regulators
Illustration summarizes the molecular mechanism and signaling pathways underlying the effect of Dis on HCT-116 cells
The mechano-chemical transduction signaling pathways participating in the production of IL-6
Proposed molecular Wnt signaling pathway in lung fibrosis during ARDS
Schematic depicting proposed pathway for the generation of proximal or distal epithelial lineages in the lung on activation of human induced pluripotent stem cell (iPSC)-derived airway epithelium via Wnt signaling
Complement activation cascades and functions
Regulation of complement activation by RCAs or parasite-expressed proteins targeting different complement components at the different steps of complement activation
PELO/HBS1L detection of PF8503-stalled 80S ribosomes activates a translation quality control pathway that includes ASC-1 (ASCC1-3), which recognizes a K63-linked polyubiquitin signal on the ribosome
(A) Feed-forward network of interactions from growth receptors to PI3K a... (B) The mTORC1 pathway feeds back to dampen PI3K → AKT1 signaling by med...
(A) Degradation and re-synthesis of the PI3K subunit p110 is driven by P... (B) Plk1 inhibition at different points along the cell cycle leads to fo...
The interaction between miRNAs and TGFB pathway in GC
The interaction between miRNAs and FSH pathway in GC
The interaction between miRNAs and apoptosis pathway in GC
Schematic illustration of the mechanism on apoptosis inducing effected of HA-based PDT
VPA inhibits LPS signaling in macrophages
VPA inhibits monocyte to DC cell differentiation
VPA induces apoptosis in neutrophils and diminishes their phagocytic capacity
VPA reduces the cytolytic activity in NK lymphocytes against tumor cells
VPA affects IL-12-, IL-15-, and IL-18-mediated IFN-γ production in NK cells
VPA induces apoptosis and inhibits IL-4 production in TγŒ¥ lymphocytes
VPA impacts the B cell differentiation into plasma cells and in the isotype switch and maturation affinity of immunoglobulins
VPA promotes the generation of Treg cells
The schematic diagram of ROS-medicate HIF-1 signaling pathway
The metabolic pathway of amino acid glutamate (a) and expression changes of related genes (b)
Schematic diagram of Œ±βT cell receptor (TCR) signaling pathway
Analysis of the PI3K/AKT signaling pathway based on the KEGG database
Representatives shown for the MAPK, PI3K/Akt, and Wnt pathways
In large pre-B cells, IL-7 receptor (IL-7R) signalling activates AKT and the Janus kinase (JAK)‚Äìsignal transducer and activator of transcription 5 (STAT5) pathway
Therapeutic targeting of glycolysis, lipid and redox metabolism in CSCs
Schematic model of LOXL2 promoting lymphangiogenesis and lymph node metastasis
Proposed mechanism of action of MR309 to decrease the expression of inflammatory cytokines and the hyperexcitability of spinal neurons after contusion of the spinal cord
Squalene biosynthetic pathways and production strategies
Pool sizes of intracellular metabolites in S
Proposed model for the impact of Metformin on FOXO3a and gene transcription in primary human fibroblasts
DEGs involved in the plant–pathogen interaction pathway in grapevine infected with L
Model for the regulation of CP biosynthesis and the attachment to PG in S
The functional network of cancer derived EVs in GC microenvironment
Illustrative diagram for exosome-mediated transfer of therapeutic resistance in the tumor microenvironment (TME)
Fibroblast growth factor receptor 4 signalling pathway in cancer
Schematic model of the effects of SIRT2/cMYC pathway in CCA cells.SIRT2 and cMYC reprogrammed the metabolism of CCA cells by up-regulating downstream p-PHDA1 and PHGDH/PSAT1/PSPH
DNA repair pathways with mutated genes highlighted
Therapies targeting cancer specific DNA repair defects
The mechanism by which GBE attenuates diabetic atherosclerosis
A schematic illustration of SAA attenuating kidney oxidative stress in 5/6Nx rats
Focal forebrain IR/IGF1R DKO eliminates signaling by receptor homodimers and hybrids in hippocampus or central amygdala
Mechanistic illustration of the effect of alcohol on the dysregulation of genes involving several metabolic pathways leading to alterations in serum metabolomic profiles
Proposed model for the induction of the Vps34-autophagy pathway in ETV6 RUNX1-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells
Scheme for metabolic flux in stimulated platelets and sites of action of small-molecule modulators
A) Regulation of expression of differentiation genes in GIST882 and GIST... B) Model for dual survival pathways and addiction to YAP in GIST882 and...
Proposed mechanisms driving localized decidualization in the cycling human endometrium
Modulatory mechanisms of TRAIL extrinsic signaling pathway by E3 ligases and deubiquitinases
The scheme of SUMOylation and deSUMOylation pathway
Schematic representation of AMPK-dependent anticancer activities of honokiol in ovarian cancer cells
Schematic diagram of the regulatory effects of H2S on PCSK9 expression and lipid metabolism
Schematic view of Scrophularia buergeriana extract (SBE) regulating reactive oxygen species (ROS) levels and the apoptotic signaling cascade
The hypoxia-inducible factor-1 (HIF-1) signaling pathway
The hypothesized pathways of volatile anesthetics induced neuropathology associated with Alzheimer’s disease
The APR signaling pathway is associated with ozone exposure and bacterial infection
Expression patterns of the most relevant genes related to hormone biosynthesis/homeostasis, perception, and signal transduction plotted within the correspondent KEGG maps (the pathway code is also indicated at the top-right of eachmap)
The networks of Ingenuity Canonical Pathways results of mRNA of APP/PS1 and SAMP8 mice brain tissues
Cellular pathway of the effects of MET + PTX-induced growth inhibition and apoptosis of PCa cells
The role of cGAS-STING pathway in anti-tumor immunity
Metabolic pathway of propionyl-CoA and methylmalonyl-CoA
Gene networks and canonical pathways generated by Ingenuity Pathway Analysis
The differential network for the pathway “Signaling by NOTCH1” in the lateral compartment
Analysis of human inner ear transcriptome over-layed on a generic human neurotrophin signaling pathway
RIG-I, MDA5, LGP2, PKR, and TLRs3/7/8 are activated during viral infection in the presence of non-self dsRNA
A schematic illustration showing anti-inflammatory responses in RAW 264.7 cells after treatment with AS-6
(A) In monocytes/macrophages and a... (B) In adipocytes, SIRT1 deacetyla... (C) In skeletal muscle, SIRT1 incr... (D) SIRT1 deacetylates Forkhead bo...
Simplified schematic depiction of the major signalling cascades in filamentous fungal cell factories
Regulation of FABP4/aP2 secretion from adipocytes
Important signaling pathways of potential therapeutic significance in patients with BTC.Abbreviations: AKT/PKB, protein kinase B; ARID1A, AT-rich interactive domain containing protein 1A; BAP1, BRCA1-associated protein 1; BRAF, V-Raf murine sarcoma viral oncogene homolog B; BTC, biliary tract cancer; Dvl, disheveled protein; ErbB1, erythroblastic leukemia viral oncogene 1; ErbB2, erythroblastic leukemia viral oncogene 2; FGFR, fibroblast growth factor receptor; FZD, frizzled family; HDAC, histone deacetylase; IDH, isocitrate dehydrogenase; KRAS, Kirsten rat sarcoma viral oncogene homolog; MAPK/ERK pathway, mitogen-activated protein kinase/extracellular signal-regulated kinase pathway; mTOR, mammalian target of rapamycin; NADP, nicotinamide adenine dinucleotide phosphate; NADPH (reduced), nicotinamide adenine dinucleotide phosphate; PDGFR, plasma-derived growth factor receptor; PI3KCA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit A; PKA, protein kinase; PORC, serine O-palmitoyltransferase porcupine protein; PTEN, phosphatase and tensin homolog; RNF43, ubiquitin E3 ligase ring finger 43; TCF, T cell factor; VEGFR, vascular endothelial growth factor receptor; Wnt, Wingless-related integration; ZNRF3, E3 ubiquitin ligase zinc and ring finger 3
Complement genes are persistently dysregulated up to six months post-TBI (A)
Example of integrated results from Upstream regulator and Downstream effects analyses in IPA indicating potential phenotypes or biological impact of TBI-dysregulated genes at 24 hr after TBI in hippocampus
a Inflammatory conditions in primary astrocytes: LPS activates NFŒ∫B that promotes the expression of (1) molecules that generate inflammation and (2) the Notch ligand Jag-1 that reduces Notch activity and consequently induce a reactive morphology in astrocytes
Schematic representation of PKZ-mediated signaling pathway
Potential candidates of miRNA-based therapy against perinatal hypoxic-ischemic brain injury
The proposed molecular mechanisms of apoptosis and autophagy induced by BOS-93 in A549 cells
Top panel: GTS-21 was unable to suppress TNF-induced secreted alkaline phosphatase in a Œ±7 nAChR and NFŒ∫B-SEAP expressing GH4C1 cell system
ANAC044/ANAC085-mediated pathway involved in stress-induced G2 arrest
MicroRNAs regulate the smoking‚Äêrelated ERBB2 signaling pathway
BTLA-associated signaling pathways (stimulatory/inhibitory) regulate the outcomes of HBV-ACLF, liver graft tolerance/rejection, liver cirrhosis and hepatocellular carcinoma
(A1) GPCRs induce GŒ±q dependent c-Src activation at the plasma membrane and tyrosine phosphorylation of NEDD4-2, releasing NEDD4-2 auto-inhibition
Summary of genes involved in the glycolate production pathway
The gene network on chemokine signaling pathway by KEGG analysis of module-related DEGs
Different sources of EVs in the cancer-to-stroma communication network
Activation of the Akt signaling pathway by ST6GALNAC1 enables tumor cells to acquire stem cell stemness
Putative mechanisms involving ET-1 system whereby MPs released under VEGFi treatment causes endothelial cell dysfunction
Illustration of the synergistic effect of SNX-2112 and TRAIL in HeLa cells
Parturition-specific signaling networks constructed using shortest paths and differential expression data
Schematic model depicting RARŒ±‚Äôs involvement in regulation of intracellular signaling, protein synthesis, and synaptic plasticity in postsynaptic neurons
(A) Ceramide (Cer) synthesis pathways and their cellular compartmentaliz... (B) Cer cell signaling. Cer are bioactive lipids upstream several pathwa...
Putative palmitoylated proteins of the mechanistic target of rapamycin (mTOR) signaling pathway
Comparison of fluxes between the wild-type case and glycan-producing strain of type EcGM3 as calculated by flux balance analysis
P-selectin expression with downstream pathways leading to a prothrombotic and/or proinflammatory state
Different pathways regulation of hippo pathway
All currently known proteins required for germling communication and fusion in N
GPs unmask cryptic variation in parallel signaling pathways and subpathways
Overview of the inflammatory mediatorsA: Inflammatory mediators with mainly proatherogenic effects are mediated by interleukin-1(IL-1), interleukin-6 (IL-6), and tumor necrosis factor-Œ± (TNF-Œ±) through nuclear factor kappa beta (NF-Œ¥B) signaling cascade
Schematic model of the TLR4/NF-Œ∫B pathway mediating miR-625-5p and COL1A1 in IDD pathogenesis
Activation of autophagy process by extracellular vesicles
The complement system has both pathogenic and protective roles in systemic lupus erythematosus
Model of mHtt aggregation, generation of ER stress and the consequent UPR protective and later pro-apoptotic responses
Core metabolism for growth on methanol with MIDs for key metabolites
Regulatory mechanism of calcium on HIF1Œ± induction
Ingenuity pathway analysis networks related to immune modulation and inflammatory response are presented in this figure (A–D)
Ingenuity pathway analysis networks related to neurological disease are presented in this figure (A,B)
In response to various stimuli such as infection or injury, mucosal epithelial barriers express a range of signals that ILC2s can integrate
Overview of the apoptosis pathway and potential targets for pharmacological modulation
Overview of the autophagy pathway and potential targets for pharmacological modulation
DEGs clustered in the PPAR signaling pathway
Schematic representation of the role of CXXC5 and molecular mechanism of KY19382 in longitudinal bone growth
Icaritin induced apoptosis through multiple and differential signaling pathways
Transcriptional coverage of penguin transcripts within the vertebrate nuclear factor kappa B (NF-Œ∫B) signaling pathway (#04064)
Transcriptional coverage of penguin transcripts on the vertebrate Janus kinase/signal transducers and activators of transcription (JAK-STAT) (#04630) (A) and vertebrate Toll-like receptor (TLR) signaling pathway (#04620) (B)
OSM signals through the STAT3 pathway and leads to IL-6 induction in ER− cells, while IL-1β induces IL-6 through the p65 pathway
Bioinformatics analysis of direct ERRŒ± target genes in mouse liver
Schematic diagram of HPV16 endocytosis and trafficking to multivesicular bodies
(A) State of the art of cellular and molecular mechanisms taking place i... (B) New molecular insights from the work published in this issue, demons...
Diagram of the Notch and APP signalling pathways
Schematic representation of the mechanism of PP26 induction of G2/M-phase arrest in HepG2 cells
PITX2 plays an oncogenic role in LUAD by transcriptionally regulating WNT3A and thus activating Wnt/β-catenin pathway
The mechanisms by which carbon-based nanoparticles induce cytotoxicity of macrophages
MyD88 played a critical role in alveolar macrophage-mediated inflammatory response to CNTs
Negative Regulation of PRR-induced signalling
Exogenous H2S restores PC-induced cardioprotection by up-regulating the HB-EGF/EGFR pathway, which activates the ERK1/2-c-myc (and fos and c-jun) and PI3K-Akt-GSK-3β pathways in the aged cardiomyocytes
Fludarabine Improves NDV-Mediated Oncolytic Viro-immunotherapyOn the one hand, the viral RNA activates the cytoplasmic RIG-I signaling pathway in the host cells to produce type I IFNs or other antiviral molecules
Biosynthetic pathways of branched short-chain alcohols and esters and their regulation in S
Reconstructed key metabolic pathways of Thermoprofundales based on eight MAGs (a)
A general summary of the NBP-involved cellular signal pathway in (a) cancer cell proliferation, migration, and apoptosis and in (b) stem cell differentiation
Signaling network of the MSC components related to protein synthesis and cancer
Systematic association of the MSC components with mTOR and DNA repair pathways
Binding of VEGFR2 with VEGFA causes autophosphorylation, which in turn causes activation of plc-γ-Raf kinase-MEK-MAP kinase and the PI3K/Akt pathway and promotes cell proliferation
Linking morphogenesis with antifungal drug treatment and drug resistance in Candida
MiniSOX9 has an oncogenic behavior in CRC
Graphical representation of organohalogen exposure to mitochondrial disease AOP
Summary of the proposed inhibitory mechanisms exhibited by WG-391D in ovarian cancer
Hub genes and module analysis of the PPI networks
Signal crosstalk in NF-Œ∫B transcriptional regulation
Lymphatic vessel functions during tumor progression
Schematic model of DHAV-1 inhibiting type I interferon signaling by hijacking the SOCS3 protein
Schematic representation of m6A function in AML
Possible mechanisms underlying the reinforcing and analgesic effects of alcohol exposure
Diagram of major H4K20-related proteins and their proposed role in DNA double stranded break (DSB) repair
Cause-effect relationship between oxidative stress and type 2 diabetes mellitus (T2DM)
(a)Insulin inhibits isoproterenol-induced lipolysis by increasing PDE3B expression via AKT
The rectangles from left to right represent 4°C, 20°C and UV-C treated fruits
Schematic presentation of the cytotoxic pathways, induced in cancer cells by the complement C5b-9, the counteractive cellular resistance mechanisms, and postulated approaches to overcome this cancer evasion
Schematic representation of the Hippo signaling pathway-YAP/TAZ in human endothelial cells
Hypothetical sequentially coupled transduction pathway leading to the activation of VRAC by hypotonicity-induced cell swelling
The biogenesis and function of ribosomal RNA-derived fragments
Schematic model of NMDAR-mediated signaling in GBM cells
Schematic representation of metabolism in tumor cells
Summary and functional network target analysis of ginsenoside Rb1, which exerts significantly anti-obesity, anti-hyperglycemic, and anti-diabetic effects on diabetes via multiple links across regulatory mechanisms and multi-target effects
Schematic representation of LC1405 neuroprotective pathway against amyloid-β peptide (Aβ)-induced toxicity
Lung adenocarcinoma treatment and emerging therapeutic potential of targeting macrophages
Biochemical reactions of the phosphatidylinositol 3‚Ä≤-OH kinase (PI3K)-Akt and Nuclear Factor-kappaB (NF-Œ∫B) pathway and its modularization
Moonlighting functions of the endothelial protein C receptor (EPCR)
Vascular endothelial growth factor (VEGF) binds to the VEGF receptor, a receptor tyrosine kinase, leading to receptor dimerization and subsequent auto phosphorylation of the receptor complex
Reprogramming of lipid metabolism under hypoxia
Schematic representation of the Notch signaling pathway
Other Notch-related tumorigenic aspects in the pathogenesis of Glioblastoma
Dual prey-inactivation strategy of the venom of C
Retrograde signalling and cellular adaptations
Endoplasmic reticulum stress (ERS)-mediated apoptosis and cancer therapy
ER stress and chemo-resistance: Role of protein kinase R-like endoplasmic reticulum kinase (PERK)
ER stress and chemo-resistance: Role of inositol-requiring enzyme 1 alpha (IRE1), activating transcription factor 6 alpha (ATF6), and glucose-regulated protein 78 (GRP78)
Signaling pathway of different DCs receptors (CLRs)
The relationship between USP6NL and the pathway
Multiple pathway stimulation of ADAM activity, leading to sAPPŒ± proliferation and notch stimulation
The proposed working model showing that stimulation of BEECs with sperm activates MAPKs components (p38MAPK and JNK; solid lines) without any effect on other downstream targets of TLR2/4 signaling pathways (ERK1/2, NFKB or IRF3; dotted line) down to the nuclear translocation of AP-1 protein which in turn regulates the transcription of pro-inflammatory genes in BEECs
SOCS induction by and inhibition of the JAK/STAT pathway
Activating p38 MAPK intersection signaling pathway
Immune evasion mechanisms associated with the PD-1/PD-L1 signaling pathway in the tumor microenvironment of lymphoma
Schematic diagram showing the two major insulin signaling pathways and the role of Mg2+ in metabolic signaling
Overview of the IL-1, IL-36, IL-37, and IL-38 receptors and intracellular signaling
The antioxidant signaling pathway regulated by quercetin
Metabolic and signaling pathway crosstalk in tissues of animals with high inherent aerobic capacity (HIAC) and animals with low inherent aerobic capacity (LIAC)
Proposed 5-HT1A receptor-mediated signaling pathway through which mGlu2/3 receptor antagonists and ketamine exert their antidepressant effects
The possible role of DhHP-6 in type 2 diabetes experimental model
Ang-II induced cardiac fibrosis mediated by periostin
Regulatory mechanisms of macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B, ligand (RANKL) induced osteoblast differentiation and survival
Regulation of the mucus production by MAPK signalling
ERK1/2 and p38 MAPK-CREB-mediated GM-CSF secretion
Schematic representation of the MEK5–extracellular signal-regulated kinase 5 (ERK5) pathway with activators and downstream effectors
Transcriptional effects in zebrafish liver after feeding with 25pct of maize substitution
Biosynthetic pathway of ginsenosides according to []
Type I and III interferon production following pathogen sensing
A schematic proposal on how toxins utilize the ER and cytosolic host factors in their transport to the cytosol in the mammalian or yeast cells
Molecular mechanisms of insulin functions and associated modifications in the hypothalamus
Signaling pathway involved in THP-1 human monocyte activation by glycomacropeptide
Signaling pathway involved in intact or papain-hydrolyzed glycomacropeptide modulation on RAW 264.7 macrophage response to lipopolysaccharide or hydrogen peroxide
Signaling pathway involved in papain-hydrolyzed glycomacropeptide modulation on HepG2 cell response to hydrogen peroxide or to high-glucose conditions
Proposed schematic depicting the signalling pathway via which TGF-β1 promotes the osteogenesis and migration of osteoblasts
Cilia-dependent regulation of PDGFRŒ± signaling pathway
Proposed model of two trans-membrane mucins (MUC1, MUC13) action in promoting hepatocellular carcinoma (HCC) growth, tumour progression and metastasis, as well as the role of MUC15 in inhibition of tumour growth and metastases (with own modifications) [,,,,,,]
Schematic diagram of cinobufagin-induced effects on hepatocellular carcinoma Huh-7 cells with mutant p53
Hypothetical G protein-coupled receptor (GPCR) heterodimeric T1R2/T1R3 taste receptors exist in a multimeric receptor complex with NMBR, IRβ, and Neu-1 in na√Øve IR expressing cells
Transfer RNA-derived fragment target genes in the Kyoto Encyclopedia of Genes and Genomes AMPK pathway map generated using DAVID software
Model of BmPGRP2 functional differentiation in host immune response to pathogens
Possible mechanisms of cancers caused by Porphyromonas gingivalis
Cilia-dependent and independent activation of Gli proteins
Proposed regulatory mechanism of estrogen in colitis-associated colorectal cancer at week 2 (A) and at weeks 10 and 16 (B)
Effects of vitamins on Alzheimer’s disease
Rg3 inhibits cell proliferation and induces apoptosis via different effector molecules and pathways, in MDA-MB-231 cell line [,]
The autophagy-A highly conservative cascaded regulatory mechanism upholds the intracellular homeostasis of the biological system
The interconnection of autophagy-related proteins in (A) neurological diseases, (B) cancer, (C) renal disease, and (D) infectious diseases
Signaling pathways in mDA neuron development
Arachidonic acid pathway (left panel) with associated impact of aspirin/non-steroidal anti-inflammatory disease (NSAID) therapy and inhibition (right panel)
The proposed schematic diagram of RLIP76 role in angiogenesis
Identification of unique pathways after treatment with SC-3–141
Schematic representation of the mechanisms of total triterpenes of the E
Interaction network showing miRNAs and their predicted and validated targets
Tumor necrosis factor-Œ± signaling in gastric cancer
Regulation of intestinal organoid formation by different growth factors
Signaling pathways involved in ICA-mediated BMSC proliferation, osteogenesis, angiogenesis, and migration
The proposed schematic representation of the immune response to MERS-CoV infection and how the invading virus is processed during an infection
Biological functions of IL-32 in inflammatory tumors
Biological functions of IL-32 in non-inflammatory tumors
(A) Detailed schematic diagram of cellular decision of proliferation and... (B) Block diagram of the theoretical model representing glucose
Metabolic profiles influence macrophage inflammatory status
BDNF induces survival-related signaling mechanisms: BDNF induces survival-related signaling mechanisms: In physiological conditions, binding of BDNF to TrkB receptor in either paracrine or autocrine signaling elicits three distinct downstream pathways
Graphical abstract shows the protective mechanism of SFN against Ar-induced damage in the kidney tissue via PI3K/Akt-mediated Nrf2 signaling pathway
Modulation of the PI3K-Akt-mTOR signaling by bioactive sphingolipids
The significance of bioactive sphingolipids in neurodegeneration
Overview of canonical and alternative Wnt signaling pathways
Overview on the principles of canonical and non-canonical NFŒ∫B pathways activation
The interplay between HPV-infected keratinocytes and the local immune microenvironment critically influences cervical carcinogenesis.HPV suppresses inflammatory signaling in the host keratinocyte
Distribution of target proteins of baicalin in the “Alzheimer’s disease pathway”
Distribution of target proteins of icariin within the “Alzheimer’s disease pathway”
Distribution of target proteins of dihydromyricetin within the “Alzheimer’s disease pathway”
Distribution of target proteins of hesperidin in the “Alzheimer’s disease pathway”
The model illustrates the mechanism for the effect of DAPT on modulating F-actin polymerization through PI3K/AKT/Cdc42 signaling by Non-canonical Notch pathway during cancer cell migration
Schematic overview of the brassinosteroid pathway components that are targeted by BPC6 in vivo
Overview of transcriptional reprogramming of the H-series strains H14, 20, 27, and 31 at 24 h post-induction of gene expression
Re-analysis of 15 selected genes by KEGGpathway enrichment
a The inflammasome as a gear or cogwheel that couples purinergic signaling with the complement cascade (ComC) in the process of HSPC mobilization
Biological pathways associated with non-synonymously mutated genes in TCL1 mice
Schematic representation of the mTOR-signaling pathway in ASD
Regulation of fatty acid oxidation, mevalonate pathway, and arachidonic acid metabolism by p53
RUNX3 and p53 act independently and in concert to elicit their tumour suppressive function
Feedback loops based on self-sustaining kinase activation or translation, hypothesized to play roles in maintaining persistent LTP and LTM
Thepotential target proteins of NF-Œ∫B protein family
Nonalcoholic fatty liver disease-Kyoto Encyclopedia of Genes and Genomes pathway and mechanisms of disease pathogenesis
Yes-associated protein and WW-domain-containing transcriptional co-activator with PDZ-binding motif is a point of convergence in signaling pathways
Schematic overview of the mevalonate pathway
Differentially expressed coat color genes in Changthangi Pashmina goat and their involvement in melanogenesis signaling pathway (Adapted from ref.)
Pervasive regulation of TLR signaling pathway by miR-146a/b family and miR-125a~99b~let-7e cluster
Mechanisms supporting BRAF inhibitor resistance in melanoma
Schematic diagram of SNG mediated action in MM cells
Model of cell cycle regulation in GCs of small follicles
A partly hypothetical model describing the characteristic shifts of balance within the sphingomyelin/salvage pathway attributed to immune low and immune high tumor subtypes/subgroups of patients
General representation of the signaling pathways involved in the antagonism of both ionotropic and metabotropic glutamate receptors in anti-cancer mediated effects
ERK1/2 regulate IL-10 transcription via MSK1/2 dependent and independent mechanisms
Mechanism of CB-R-mediated antitumor activity in breast cancer cells
Mitogen-activated protein kinase (MAPK) signaling pathways in model fungi
Multiple levels of MKP regulation in fungi
The protein C activation by the thrombin-thrombomodulin complex and the cytoprotective function of Activated Protein C (APC) in ischemic heart disease and heart failure
Rationale for combining immune checkpoint inhibitors with antiangiogenic drugs, anti-tumor immune response modulation adapted from Amin et al
Proposed mechanical cues regulates Hippo signaling pathway in gastric tumorigenesis
The schematic diagram of EGCG anti-tumor mechanisms based on reverse docking
Regulation of osteoblast proliferation and differentiation by transcription factors
Calvarial bone development and suture closure
Schematic illustration of rapamycin (mTOR) signaling pathway
A diagram of microRNAs and their involved pathways to cancer hallmarks
Transcriptional changes of type I interferon (IFN-I) signaling pathway members in the cerebellum of canine distemper virus (CDV)-infected compared to control dogs
The inhibition of NFŒ∫B signaling can occur at different steps of its activation pathway
Graphic summary for nifedipine-induced lipogenesis on renal tubular cell
Gene expression, for a clustered subset of genes in the cell cycle pathway, is up-regulated
Gene expression, for the clustered subset of genes in pathways in cancer, is up-regulated
A novel IL-1β-ILC3-IL-2 circuit is essential for the maintenance of Tregs and immunologic homeostasis uniquely within the small intestine
Working model of stiffness-dependent calcium response for neutrophils on HUVECs
(a) Schematic representation of the major components of the endosomal pa... (b) The contents of exosomes may serve as biomarkers for disease—some of...
Proposed mechanism of thyroid enlargement in patients with homozygous INSR mutation
Hypothalamic regulation of energy homeostasis in healthy (blue) and obesity (pink)
Schematic of the Insulin Signalling Pathway and insulin resistance
Schematic representation of the physiological generation and function of lipid mediators in immunity
Complexity of GAL/SPX and receptor systems and pharmacological properties of SG2A
Schematics presenting mechanisms of actions of approved and selected experimental cytokine and cytokine receptor agonists and antagonists
The molecular pathways targeted by the TCMs covered in this review are summarized
Model of Uxe function in biosynthesis of cell surface polysaccharides in S
Visualization of resulting networks from Min-cut on the pathway of AD
a Illustration for cut-edges and the CTGs in AD pathway from KEGG
Schematic representation showing that β‐arrestin2 (ARRB2) negatively regulated NOD2 signalling pathway through the association with TRAF6 in cerebral ischaemia/reperfusion injury
After synthesis histones H3 and H4 interact in the cytosol with common folding chaperones HSC70 and HSP90, with H3 being mono-methylated on K9 co-translationally by SetDB1
Possible mechanisms of the anti-tumor effects of bitter melon
Overall possible mechanism of CS-PAC-AgNPs induced mitochondrial apoptotic signaling pathway
Mechanisms involved in the prooncogenic activation of the NRF2/KEAP1 pathway
Process and regulatory mechanism of autophagy
Schematic model for Cbl-b in BCR- and CD40-mediated signaling pathways Activation of CD40-dependent signaling pathway is mediated primarily by several TNFR-associated factor (TRAF) protein family members including TRAF2, 3, 5, and 6
Representative working modes of mutant p53 GOF
Therapeutic strategies targeting mutant p53
Schematic representation of the cellular functions of the PLAC8 up-regulated genes
Map of molecular mechanisms involved in SRPK1 regulation in the apoptosis of intracranial aneurysm smooth muscle cells
Dauer signalling pathway model proposed for Haemonchus contortus
Reversion of HIV-1 latency regulated by DCs
Modes of MUC1 control of cellular inflammatory signaling pathways
A schematic representation of the purinome in the MM environment under bone marrow niche metabolic reprogramming
Schematic depiction of the CD38/CD203a/CD73 adenosinergic pathway as a major mechanism of the acquired resistance to anti-PD-1/PD-L1 blockade within the BM niche
Network analysis of Ly6D, Ly6E, Ly6K, and Ly6H genes
Role of immune cells and TNF family members in regulating drug-induced liver damage
Metacore™ map showing the signaling context of the genes contained in the “Vascular endothelial cell damage in SLE” pathway
Schematic representation that hypothesizes the effects of ethanol (A), THC and/or OEA (B) on neurotrophic signaling pathway via AKT and ERK1/2, and its neurogenic response in the hippocampus
Positive and negative feedback signals for neuronal polarization
Enriched genes from the ANOVA statistically significant disease status gene list (p-value < 0.05) found in the KEGG Alzheimer's disease pathway (hsa05010) [Kanehisa and Goto, ; Kanehisa et al., , ]
Deletion of both cytosolic superoxide dismutases impacts metabolite concentrations and enzyme abundance of TCA cycle (A), glycolysis (B), and pentose phosphate pathway (C)
Schematic depicting the sensitization mechanism of CsA to crizotinib
Schematic overview for the roles of miR-24, miR-23a and miR-145 in TGF-β signaling in AKI
Differential regulation and effects of glycolysis induction in GM-DCs upon stimulation over time
A proposed mode of action for RHOA to maintain TE characteristics in the expanding blastocyst
Schematic view of signaling events elicited by LPS in RPE cells
MiR‐125b‐protein and protein‐protein interaction network of differentially expressed genes, with particular focus on AHSG (fetuin‐A), FGF‐23, and TNFRSF11B (osteoprotegerin)
Molecular mechanisms of modifiable risk factor mediated induction of cytokines involving subsequent activation of CREB, resulting in pancreatic cancer growth and progression
Graphical sketch of the expression and inhibition of different pathways
Role of the classical and terminal complement pathways in cold agglutinin disease and target levels of complement inhibitors
Proposed Schematic diagram of Mda5 signaling pathway in Teleost based on a Mammalian Model
Autophagy initiates host immunity and Toxoplasma immune evasion
Targeting of host gene expression by Toxoplasma gondii
Schematic showing mechanisms underlying morphine tolerance
Comprehensive overview of the role of Clusterin on apoptosis-related events in cancer cells
IFN-γ pathway associated with differentially expressed genes between SRHIC and WRHIC purified CD8 T cells
Evolutionary conservation of the IIS pathway
Beta-adrenergic signaling pathway in prostatic cancer
Schematic representation of signal contributes to CSC phenotype
Model of comfrey‚Äôs mode of action by interference with the NF-Œ∫B signaling pathway
Endocrine and pharmacological regulation of penile erection
Schematic Illustration of a Developing Therapeutic Decision Tree for Ductal Breast Cancer with Emphasis on the TNBC Subtype
The mechanistic scheme of lncRNA lnc-TALC in GBM
A proposed model of participation of SNHG1 in the regulation of signaling pathways that contribute sorafenib resistance in HCC cells
The pathway of direct action target of TWH (the yellow is the compound, the magenta is the target, the green is the signaling pathway, MOL0005828 represents nobiletin compound, MOL003217 represents Isoxanthohumol compound, MOL003182 represents (+)-Medioresinol di-O-beta-D-glucopyranoside_qt compound, MOL003199 represents 5,8-Dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3)-coumarin compound, MOL003187 represents triptolide compound, MOL000422 represents kaempferol compound, MOL000449 represents Stigmasterol compound, MOL000358 represents beta-sitosterol compound, MOL000296 represents hederagenin compound.)
Putative suppressive pathway of Pj-ME in displaying its anti-inflammatory response
Mechanisms of Annexin A1 in inflammation
Mechanisms of Annexin A1 in tumorigenesis
Model depicting how novel drugs targeting the Y‐box binding protein‐1 (YBX1) activation pathway overcome drug resistance
The molecular mechanism diagram showed that miR-27b-3p played an important role in atrial fibrosis and the occurrence of AF by regulation of the signaling pathway of Wnt/β-Catenin through targeted Wnt3a
Schematic illustration of angiogenesis signaling pathways induced by OS
Schematic diagram of the proposed molecular mechanism for LPS-induced downregulation of StAR expression and progesterone production in pGL
(Kyoto Encyclopedia of Genes and Genomes (KEGG)) pathway enrichment (P < 0.05) representing neuroactive ligand-receptor interactions from lepa rescue compared to control microarrays.
Diagram showing the main paracrine and dichotomic autocrine functions of the IL-6/JAK/STAT3 pathway in the pathophysiology of skeletal muscle
“Cytokine–cytokine receptor interaction”, “steroid biosynthesis” and “cell cycle” pathway and the identified regulator
HSVs modulate antiviral mechanisms related to cell death in non-immune cells
HSV proteins modulate key steps in interferon-related pathways
HSVs interfere with antiviral processes in innate immune cells
A potential role for TXNIP in HG-mediated RPE dysfunction
A model for the functional interplay of IL-21 with type I interferons in the response to MRSA
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway network for Kashin-Beck disease (KBD)-related genes
Œ±-Synuclein and the modulation of lipid signaling
Diagram showing differentially expressed genes in BXW-resistant and BXW-susceptible genotypes of banana after inoculation with Xanthomonas campestris pv
IPA prediction networks associated with Ginsenoside Rg1 protective activity on AD mice in this study
Activation of Spry2 (conserved cysteine-rich region in green) in response to receptor tyrosine kinase (RTK) stimulation is induced by Src kinase (Y55 phosphorylation, Y53 for Spry4) followed by phosphatase recruitment (PP2A) which dephosphorylates serines 112 and 115
Interaction mapping of overlapping proteome changes in astrocytes treated with GBM a -stem and b -diff EVs
BCR-ABL, BCR-FGFR1, and BCR-RET all activate STAT, MAPK, and AKT, while BCR-JAK2 only activates the STAT pathway, and signaling by BCR-PDGFRA remains to be elucidated
MEF-2 is also activated by PI3K/AKT pathway which activates mTOR as a downstream target and also increases the transcription of MyoD and MEF-2 along with other transcription factors
Scheme of the immune system in HCC surveillance and the metabolic effects of alcohol exposure on hepatocyte
Role of macrophage, fibroblast and endothelial cell pathways in MAIT cells
Natural killer cell signaling pathway of MAIT cells in comparison with conventional T cells
T helper cell differentiation pathway of MAIT cells in comparison with conventional T cells
Downstream signaling pathway of adiponectin
The role and expression of proteins identified by proteomic analysis within NAD+ metabolism and signaling pathway
Transcriptome analysis results of nuclear factor erythroid-2 related factor 2 knockdown
GSK-3β/Snail pathway is involved in the synergistic effect of BAY 87-2243 plus HDAC inhibitors
Proposed models of CST1 participating in the signaling pathways.Notes: CST1 was involved in GSK3, AKT, and IL-6 pathways
GPCR trafficking and compartmentalized signaling
Mechanistic pathways underlying reverse cholesterol transport from macrophages to liver
Hypothetical model of the role of FcŒºR in central deletion and B cell repertoire selection
Schematic model of the Wnt/β-catenin signaling pathway regulated by PARG gene silencing during BaP-induced lung cancer
IGF-PI3K-AKT-FOXO pathway of insulin signaling
Regulation of gene expression (A) and protein phosphorylation level (B) of ILP (IGF ‚Üí FOXO cascade) during different diet stress
Influence of TGF-β1 on the balance between the canonical WNT/β-catenin signaling and PPARγ
DEGs relevant to the “protein processing in endoplasmic reticulum” pathway under group “D vs
The annotated functions of the extracted pathway network
The role of lipotoxicity in promoting insulin resistance in skeletal muscle
Synthesis, activation, secretion, and downstream actions of MGP (matrix Gla protein)
Schematic representation of the phenylpropane pathway
Enrichment analysis of genes transcriptionally related to morphometric similarity
Model of NLRP3 inflammasome activation involved in OA-induced ALI rat model
Generalised mechanism of chimeric antigen receptor (CAR) signalling provided by CD3‐ζ ITAMs and a costimulator domain
Molecular biological features in the adrenal gland of Hatano rats
The LSD1–NOTCH–ASCL1 Axis in Small Cell Lung Cancer (SCLC)
T10 inhibited NF-Œ∫B activity via miR155-5p/SHIP1 axis
Illustration of proposed effects of the phosphoinositide 3‚Äêkinase (PI3K) pathway inhibition on the heart in the setting of anthracycline cancer therapy
Fatty livers demonstrate a premalignant signature
. RBC cAMP-PKA-dependent pathway and AT1R vs β-AR dimer/complex.
Overexpression of PIN1 induces the expression of PTOV1, which suggest that PIN1 might be the upstream protein which regulates the expression of PTOV1
Effects of flavonoids on the expression of MMP and ADAMTS in osteoarthritis
A schematic diagram for the inhibitory mechanism of CYC116 in mast cell activation
The possible site of action of beta (β) asarone in apoptosis, cell proliferation and growth
The possible site of action of A. calamus and/or its bioactive phytochemicals asarone (alpha (α)-and, beta (β)-asarone) in tumor cell metastasis, invasion, migration and angiogenesis
A brief summary of the possible mechanisms of KSHV-mediated pathogenesis at the cellular level
Diagrammatic model summarising the proposed bimodal Wnt signalling regulation by DYRK1A, as reported in Figs –
Expression of the NCRs and their Ligands
Irradiation-induced retraction and death of endothelial cells
Potential cellular pathways and major players for the induction of the immediate early genes egr (a) and c-jun (b), and downstream targets, with focus on pathways previously linked to learning and memory in honey bees [, , , ]
Interconnection of the pathways studied, the genes in which we have measured expression and connection to mitochondrial respiration
Reelin signaling pathway in Golgi Dynamics and morphology
Upstream and downstream of mTORC1 and mTORC2
Molecular genetic pathways in long-term epilepsy-associated tumors (LEATs) and pediatric type diffuse low-grade glioma (DLGG)
A hypothetical model for the role of thrombomodulin (TM) in mitogen-activated protein kinases (MAPKs) signaling: Thrombomodulin regulates the activation of MAPKs under various pathophysiological conditions
Schematic detailing the relationship among CaMKII-, BDNF-, and NMDAR-inducing LTP and morphine tolerance
Bone morphogenetic protein (BMP) signaling pathway and inhibition by Noggin
Network analysis of proteome datasets in M1 polarized (vs
Network analysis of proteome datasets in M2 polarized (vs
Schematic representation of main signaling pathways activated by growth factor signaling through receptor tyrosine kinases (RTK) and the importance of Mg2+
Negative regulation of the TRAIL-driven pathway
Mechanisms contributing to regulation of tumor clearance by effector cells
Protein–protein interaction (PPI) network in muscle wasting in cancer cachexia
MicroRNA-regulated networks in muscle wasting during cancer cachexia based on meta-analysis data
A classical downstream G protein signaling pathway (L, ligand; CM, cell membrane; GDP, guanosine diphosphate; GTP, guanosine triphosphate; AC, adenylate cyclase; cAMP, cyclic adenosine monophosphate; ATP, adenosine triphosphate; PKA, protein kinase A; PLCβ, phospholipase Cβ; PIP2, phosphatidylinositol 4,5-bisphosphate; DAG, diacylglycerol; IP3, inositol-1,4,5-trisphosphate; ER, endoplasmatic reticulum; Rho, Rho factor; PKC, protein kinase C; GEF, guanine nucleotide exchange factor)
(a): Constitutive B2R-TP interaction exists at the plasma membrane and nuclei implying possible B2R-TP association early during ontogenesis
Model suggesting the relationships between Th17, Th1* and cTh1 populations and their potential roles in post-vaccination immunity, LTBI and active TB
Representation of the genes in glycolysis, pentose phosphate pathway, and the TCA cycle
Schematic drawing of the details of the signaling pathways of five major cardiomyopathies
Schematic drawing presents the detail signaling pathways of endometrial carcinogenesis
Functional pathways analysis reveals networks of molecular interaction and a potential mechanism of subgroup TNC overexpression in pediatric gliomaPathways analysis was performed to evaluate the biological functions and interactions of differentially expressed genes between TNC cDNA and shRNA cell lines (Log2Fold Change > 2 or < − 2, adjusted p-value < 0.05)
The STAT3 signaling pathway in cancer cells
Schematic indicating the pathway from Micronucleus formation to activation of the cGAS-STING pathway, and canonical and non-canonical routes to Type I interferon response
Metabolic dysregulation in GC‐derived B‐cell lymphoma
Aberrant BCR signaling in GC‐derived B‐cell lymphomas
Hypothetical model of CLIP‚Äê170 controlling Met RTK recycling in migrating cells
The PI3K/Akt/mTOR signaling pathway is involved in apoptosis and autophagy induced by Rk3 in esophageal cancer
Metabolomic analysis of in vitro effects of OPC-163493 in HepG2 cells
Schematic drawing showing proposed mechanisms of action of Curcuma longa (curcumin)
Inositol phosphate (IP) signaling pathway in S
A schematic diagram explaining how TRPC3 acts as an anti-apoptotic regulator via RASA4-MAPK pathway in MDA-MB-231
Proposed model for ANXA2 regulation of AKT activation
The insulin signaling pathway under physiological condition
The attenuation of insulin signaling pathway in insulin resistance condition
Schematic representation of the MAPK pathway in melanoma
Schematic reconstruction of the events triggered in the retina by hyperglycemia and reinforced by oxidative stress in a vicious cycle
Genetic and molecular mechanisms conferring resistance to SMO inhibitors
Therapeutic targeting of oncogenic HH/GLI signaling in cancer cells resistant to SMOi
Overview of Hedgehog pathway in absence (a) and in presence (b) of HH ligand
The cytotoxin-associated gene A (CagA) deregulates intracellular signaling pathways in B-lymphocytes in tyrosine phosphorylation-dependent and -independent manners to initiate the lymphomagenesis of Helicobacter pylori (HP)-dependent gastric mucosa-associated lymphoid tissue (MALT) lymphoma
The proposed model of CXCR7-EGFR crosstalk and its effect on the MAPK signaling pathway
Purported mechanisms of action of flavonoids with effects on glucose metabolism: AMPK, AMP-activated protein kinase; CHO, carbohydrate; GK, Glucokinase; GLUT 4, Glucose transporter type 4; GNG, Gluconeogenesis; GS, Glutamine synthetase; IRS-1, Insulin receptor substrate 1; JNK, c-Jun N-terminal kinases; Ox, Oxidative; PI3/AKT, phosphatidylinositol 3-kinase (PI3K) and AKT/Protein Kinase B signaling pathway; SGLT, Sodium-dependent glucose transporter; (+), increase, activation; (‚àí), decrease, inactivation
The mechanism of PDCoV N protein interfered with the type I IFN response
Schematic representation of the DA-induced ascorbate release signaling pathway in the retina
The role of autophagy on biliary epithelium differentiation and homeostasis
The circadian rhythm pathway identified as one of the significant pathways by the IPA
Schematic diagram of the HER4-JAK2-STAT5 pathway modeled in this paper
(a) By KEGG pathway enrichment analysis, ANXA2 upregulated filopodia pat... (b) By KEGG pathway enrichment analysis, ANXA2 upregulated focal adhesio...
Superimposing mTOR signaling subgraphs from KEGG and WikiPathways
Siglec-7 mediated inhibition of NK cell cytotoxicity towards tumor cells
Diagram of the mechanism of salidroside-induced apoptosis, cell cycle arrest and suppressed invasion of osteosarcoma cells via inhibition of the JAK2/STAT3 signaling pathway
Acute methamphetamine (Meth) effects on altering astrocyte activity are mediated by TAAR1-coupled signaling and K+ channel dysfunction
Model: The role of secCl within the tyramine/leucokinin diuretic pathway
The signalling pathways of ‘phosphatidylinositol signalling system’ and ‘inositol phosphate metabolism’ indicate the modulation of tumour markers and are related to the outcomes of osteosarcoma
Schematic of the PI3K/AKT signaling pathway
Effect of the PI3K/AKT signaling pathway on gynecological tumors
Small molecule inhibitors and the ALK-Smad signaling pathway
Schematic illustrating the mechanism in which elevated HP induces apoptosis in RGCs through the regulation of the NGF signalling pathway
Cell surface and endosomal signaling pathway of TLRs
TLRs-signaling in microglial cells in different neurodegenerative disease progression
Polyphenols modulating upstream (TLR activation) and downstream (different kinase and transcription factors) pathway of surface and endogenous TLR to reduce or demolish pro-inflammatory cytokines and type I interferon generation
Suggested mechanism of rFlaA:Betv1-mediated mDC activation
Overview of the main cellular protein clearance mechanisms, the ubiquitin–proteasome system (UPS), and the autophagy pathway
Mechanisms of YAP regulation in early stages of prostate cancer
The Hippo pathway regulation of advanced prostate cancer
YAP/TAZ regulate prostate cancer stem cells (PCSCs)
The heme activator proteins (HAP) complex
The Ras-cAMP/PKA Pathway in yeast and mammalian cells
The acute phase response (APR) is central to the FL induced response in skin, brain, and liver of all three model organisms
Epidermal growth factor receptor (EGFR)/EGFR variant III (EGFRvIII)-dependent biological signaling pathways
Epigenetic mediators involved in the establishment and erasure of histone post-translational modifications and DNA methylation, as described in the text
Proposed model for miR-130a downregulation of HCV infection
Genetic mutations, HIF-1Œ± activation and metabolism of RCC
PPI network for the upregulated genes in the AMPK signaling pathway
Cyclin D1–CDK4/6–Rb pathway in breast cancer
Pathway analysis of differential genes: the PI3K-Akt signaling pathway
Functional prediction of key lncRNA-mRNAs network
Overexpression of IL-6 and its potential negative consequences on the viral immune response
Signal pathways involved in LPS, IFN-γ, and CEA-AGE induced proinflammatory mediator expression via hydrogen peroxideAfter binding to their respective receptors, LPS, IFN-γ, and AGEs lead to the activation of NADPH oxidase and subsequent superoxide production and conversion to hydrogen peroxide
Schematic representation of intracellular signaling pathways that are involved in the regulation of innate immune responses against IAV
Proposed mechanism of PDGF effects in periosteum derived progenitor cells and its interaction with BMP2/Smad signaling
The regulatory mechanism of BMX-ARHGAP in the properties of GC stem cells
Proposed model for the interaction between miR-30a-5p, CD73, and TNFR2 and inhibition of the AKT/ERK pathway to induce G0/G1 phase arrest
Cend1 induces the p53-Cyclin D1-pRb signaling pathway resulting in cell cycle arrest at the G1/G0 phase of the cell cycle
Oxidative stress and vascular implications in metabolic syndrome
Hypothetical mechanisms by which the esophageal microbiota participates in the pathogenesis of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC)
The mechanisms of protection against enteroinvasive bacteria (Salmonella and Shigella)
The red and green nodes represent the upregulated and downregulated genes, respectively
The green nodes represent downregulated genes
Apoptosis Signaling During Arbovirus Infection.Arboviruses exert their effect on apoptosis through different signaling routes
Apoptosis Signaling During Influenza A Virus Infection.IAV infection affects apoptosis in early and late infection
UPR Signaling During Influenza A Virus Infection.Upon IAV infection, BiP is released from UPR proteins (e.g
The mechanisms of macrophage-mediated resistance to chemotherapy.The pathways responsible for the tumor-promoting function of TAMs after chemotherapy and chemoresistance include the increased recruitment of immunosuppressive TAMs, the pro-tumor polarization, the reduced T-cell cytotoxic response, the activation of anti-apoptotic programs in malignant cells
Molecular factors involved in cell migration
Atypical PKCs control actin cytoskeleton via Cofilin activation
Acute phase response network: The acute phase response was the most-significantly represented pathway common to all CAPN5-NIV stages
Schematic of the regulatory mechanism of miRNAs in TLR signaling
ERM structure and function in immune cells
Molecular pathogenesis of Epstein-Barr virus-positive NK/T-cell lymphoma
The predicted metabolic pathway of lignocellulose-derived inhibitors
An integrated gene interaction network built for genes related to wing dimorphism
Schematic representation of 17β-Estradiol induced estrogen receptor-alpha, -beta, and G-protein-coupled estrogen receptor signaling
(A) Dysfunctional subpathway (path:04020_1) of calcium signaling pathway... (B) Annotation of genes in path:04020_1 to the original calcium signalin...
Immunogenic Cell Death (ICD) and Tolerogenic Cell Death (TCD)
The scheme for the involvement of the mitochondrial apoptosis pathway in BA6-induced cytotoxicity in A549 cells
Target sites of therapeutics along the pathogenetic pathway of celiac disease
Effect of chronic treatment with PDF and addition of AlaGln on individual pathways, incl
Sublytic C5b-9 promotes tumor growth and survival by activating several signaling pathways
The main O2-sensing pathways described in plants (identified in Arabidopsis and hypothesized to be present in M
ER stress is sensed by three ER transmembrane proteins, ATF6α, IRE1α, and PERK, which are crucial for mediating the adaptive and apoptotic signaling of the UPR
The saturated free fatty acid palmitate, and other toxic lipids such as lysophosphatidylcholine (LPC) are known to activate the three UPR sensors
Mitochondria and ER in activation of the NLRP3 inflammasome
Diversity of the effects of DJ-1 in cell
Mapping of hits in the MAPK signaling pathway
Receptor signaling pathways upstream of TRAF6
Inflammatory loops in the EIME of psoriasis
The regulatory mechanisms of the IL-17–TRAF6 pathway
Schematic representation of the signalling pathways and deletions investigated in the current study
Possible mechanisms responsible for the effect of Nox on SAP-associated cardiac injury
UME prevented hyperlipidemia by up-regulating the AMPK pathway and regulation of lipid metabolism
Red lines show inhibition, and green lines indicate activation
Schematic representation of Wnt signalling pathway components reported to be mutated in disorders of bone development and skeletal homeostasis
Protection effects of Aucubin (AU) against lipid accumulation and inflammation in tyloxapol induced hyperlipidaemia mice and apoC‐III induced differential 3T3‐L1 cells via activating Nrf2/hemeoxygenase‐1 (HO‐1) signalling pathway
SUMOylation‚Äêmediated signalling pathway of cardiac hypertrophy
Schematic model of IL‐1β‐ and Fn‐fs‐mediated ADAMTS‐12 and ‐7 stimulation by Runx2 and Wnt/β‐catenin signalling modulation in OA‐SF
Proposed signaling pathway for LPI in cardiomyocytes that contributes to exacerbation of I/R injury
mTOR signaling pathway regulated autophagy and EMT
Beclin-1 signaling pathway regulated autophagy and EMT
P53 signaling pathway regulated autophagy and EMT
The integrin signaling pathway regulated autophagy and EMT
WNTs signaling pathway regulated autophagy and EMT
TGF-β signaling pathway regulated autophagy and EMT
Schematic representation of telomerase regulation and telomere elongation pathway
The immunosuppressive effect of the tumor microenvironment
A proposed model relating canonical and non-canonical Wnt signaling with teneurin-3 expression
A schematic presentation of the Wnt/β-catenin signaling pathway and the drugs that target this pathway in DTF
Schematic representation of the mutIDH1 and mutIDH2 pathways and molecular mechanisms related to oncogenesis
Outline of the main altered pathways in SiNETs
Directed acyclic graph (DAG) of the 10 most enriched Gene Ontology (GO) terms and cytokine–cytokine receptor interaction pathways based on KEGG analysis
A summary of the regulation network of Ids in heart development is shown
Model of the effects of the growth factor Wnt in receptor-mediated endocytosis (micropinocytosis) and in receptor-independent endocytosis of proteins from extracellular fluids (macropinocytosis)
Signaling pathways involved on induction of endoplasmic reticulum (ER) stress
Signaling pathway explains how PERK activation affects CREB signaling and memory impairment
Model of the signaling pathway for membrane glucocorticoid receptor-induced endocannabinoid synthesis
Various regulatory mechanisms of MALAT1 in different diabetes-related complications
A scheme describing the effects of dimensionality (top left) and the cell malignancy potential (bottom left) on lipid species amounts in the MCF10A breast cancer in vitro model
The role of RNF8 involves in DSB signaling pathway
Probable molecular mechanistic pathway of ruthenium baicalein complex
Neuroprotective effects of resveratrol in AD
TNFŒ±-mediated necroptosis aggravates IRI in the fatty liver by regulating the inflammatory response
IPA network analyses of the 40 deregulated genes that we obtained from COMPARE analysis (see ) revealed the reconstruction of (A) NF-Œ∫B network pathway and (B) HIF-1Œ± network
Implication of hexosamine biosynthetic pathway on the NLRP3 inflammasome
EGL-9 inhibits the HIF-1 target NHR-57 from reducing RAS/MAPK signaling through a DELTA/NOTCH-induced negative feedback loop
The schematic model demonstrates that circANKS1B regulates FOXM1/Slug pathway by serving as a sponge for the miR-149 in colorectal cancer metastasis
The relationship of the three diseases at gene, pathway, module, and function levels and the biological mechanism of T2DM, CML, and PCa
Schematic of the proposed mechanism underlying TRPA1-mediated CMF transdifferentiation and cardiac fibrosis after MI injury
Changes in PUFA metabolomes are conserved across pharmacological and physiological models of skeletal muscle injury
The JAK-STAT signaling pathway is involved in several processes.This figure was made with Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License: https://smart.servier.com.The presence of the ligand leads to receptor dimerization
Functional analyses of five core clusters
Signaling pathway mediating cardiovascular protection of OT
Schematics illustrating the possible neuroprotective mechanisms of BDNF in the hyperglycemia-induced neuroinflammation
Three example models in the CODA-ML format
a Construction of the GQD compound-putative target network
Wnt signaling deregulation in the aging brain and in AD
The effects of abnormal DA release and stimulation of DA receptors on proteasome and autophagy
STRING-generated interaction network between genes that belongs to the “response to hypoxia”, “response to organic substance”, “response to protein stimulus”, “transforming growth factor β receptor signaling pathway” and “transmembrane receptor protein serine threonine kinase signaling pathway” GO BP terms
Functional interaction (FI) between differently expressed genes that belongs to the “response to hypoxia”, “response to organic substance”, “response to protein stimulus”, the “transforming growth factor β receptor signaling pathway”, and “transmembrane receptor protein serine threonine kinase signaling pathway”
Polycystin-associated pathogenic mechanisms in human diseases
Schematic view of the ERK pathway in response to growth factors, hormones, and mechanical stress
The potential roles of aberrant activations of MAPK and PI3K signaling pathways in pathogenesis of PWS/SWS
The mechanism used by EGCG to promote cancer cell growth arrest and apoptosis
Interaction network of proteins involved in cancer, immune system, and signal transduction pathways
The mechanism of simvastatin in alleviating endothelial dysfunction under oxidative stress
Schematic diagram of the interaction between TNF-Œ± and the Hippo signalling pathway
Effects of flavonoids on impaired insulin signaling
Regulation of Wnt/β-catenin/c-Myc signaling pathway
Roles of c-Myc in colorectal cancer (CRC) organoids
Pathways of EGF mediated protein synthesis and PDCD4 degradation
EGF and TPA mediated pathway to phosphorylate serines in the SCFβTRCP recognition site of PDCD4-protein in Huh7 hepatoma cells
Representative summary of the non-glycolytic roles of GAPDH
Some common metabolic features of adult stem cells are essential for the maintenance of their quiescence, number, proliferation potential, and differentiation ability
The intensity of information flow through the mTORC1-signaling pathway defines the fate of quiescent adult stem cells
Scheme of the effect of pioglitazone on CKD-mediated ER stress in CKD-MSCs
BRO modulated virus-induced activation of the interferon response
BRO modulation of RV-induced NFkB target gene expression
BRO priming of interferon response pathway in the absence of virus
BRO priming of NFkB target gene expression in the absence of virus
RNA granules and caprin-1-associated tumorigenesis
Model of activation of the PI3K/AKT signalling pathway in mink uteri in activated versus diapause states
Model of activation of the prolactin signalling pathway in the mink uterus in activated versus diapause states
The role of T-cell suppression and immune checkpoint blockage in tumor and organ rejection
Interplay of major zonation signaling pathways
T-cell receptor (TCR) binding to antigen-loaded MHC-II triggers T-cell initial activation
Schematic representation of the insulin signaling pathway and the modulation of this pathway by cannabinoid receptor type 1 (CB1R)
The PI3K-AKT signaling pathway which was achieved by DAVID pathway analysis
The Hippo signaling pathway which was achieved by DAVID pathway analysis
Evolution of erlotinib resistance in CD166+ OSCs
Schematic representation of the deregulated metabolic pathways in AML
Network view of infected dendritic cells
Relationship between middle-age obesity, glutamate excitotoxicity and increased risk of Alzheimer’s disease
Note: (A.) The potential liver injury components urate-lowering Chinese med... (B.) The pathways are represented by green diamond. The targets are i...
hMSCs promote tumor growth via MAPK signaling pathway and metastasis by EMT in HCC
Comparison of nucleic acid signalling pathways leading to type I interferon (IFN) production in an autoimmune disease and bacterial infection
Anti-inflammatory and antioxidant mechanisms of neuroprotection and neuronal function by ursolic acid
Estrogen receptor (ER) activity in breast cancer - canonical (classical; ligand-mediated) and non-canonical (alternative; ligand-independent) pathways of ER activation
Temporal dependence of G2/M DNA replication checkpoint mechanism on the G1/S transition mechanism
Scheme of role of 67-kDa LR in vasogenic edema formation induced by SE based on the present data and previous reports (, ; ; )
Modulation of tumor immunity by radiotherapy and immune checkpoint blockade
Schematic representation of IRFs in the TLR and IFN pathways
The lncRNA/pseudogene–miRNA–mRNA ceRNA network in CRC
miR-15/107 family targeted genes in cell cycle KEGG pathway calculated by miRPath v3.0 web-server
Schematic representation of a potential nuclear factor-Œ∫B activation pathway obtained by RNA-sequencing analysis in canine diffuse large B-cell lymphomas
Receptor signaling pathway and recruitment of IL-1RAcP
Part of the plant MAPK signaling pathway
Functional significance of several key genes from four KEGG pathways differentially expressed in female and male magpies
The cartoon model of METTL14-P2RX6-Ca2+ −p-ERK1/2-MMP9 axis signal on RCC cell migration and invasion
a Metabolic routes for butyrate and acetate production by direct conversion from carbohydrates
Spatial regulation of non-amyloidogenic and amyloidogenic processing of APP
Involvement of LOAD risk factors at the BBB
Impact of flight condition on expression of crystallins in the network of proteins associated with ophthalmic disease as defined by Ingenuity Pathway Analysis (IPA, https://www.qiagenbioinformatics.com/products/ingenuitypathway-analysis)
Schematic drawing of the suggested intracellular signaling pathways of LIF and OSM receptors in osteoblasts mediating expression of osteoclastogenic factors, osteoclast formation and bone resorption
Signaling pathway based on the literatures we reviewed
CSC signaling pathways which are regulated by BRCA proteins
(A) Selected signaling crosstalk of MAPK and MST2/Hippo signaling, energ... (B) Spatial regulation of ARAF during epithelial differentiation by the...
Results of Pancancer Pathway Panel analysis
IL-6 production by blood leukocytes is altered in the RA-like PsoA patient in response to immune activators
The role of type I interferons in the cytotoxic TLR-TNF signaling network
Proposed model for an auto-regulatory feedback loop between the miR-17-92 cluster and the Wnt/β-catenin/LEF1 signaling pathway
QGS regulates Gas6/Axl by inhibiting the binding of Gas6 and Axl, thus inhibits PI3K, AKT, and NF-Œ∫B pathway, and QGS decreasing expression of NF-Œ∫B nucleus, then inhibiting tumor cell invasion and migration via reduces the expression of MMP2 and MMP9
Hypothetical signaling pathway related to heterogeneous cytoplasm-induced suppression of the multi-ovary gene
The negative regulators of JAK-STAT signaling
The ERK signaling pathway was hyperactivated in the patient's tumor tissue
Signaling pathways implicated in different categories of breast cancer
The interaction between tumor microenvironment components, including stromal cells, and tumor cells leads to enhanced cell growth, proliferation, angiogenesis and invasion
15d-PGJ2 regulates adipocyte differentiation and osteoblast differentiation via a PPARγ-dependent pathway
Focal adhesion pathway (A) and HIF-1 signaling pathway (B) altered in a CRC
—Diagram of the subset of PSGs that are involved with cellular respiration in (A) the Krebs cycle or (B) the oxidative phosphorylation pathway
After entering a cell, viral genetic material may be recognized by one or more of the host’s PRRs
A model for the regulation of T cell-mediated adaptive immune responses to apoptotic cells
Illustration of DEGs encoding the key enzymes of the ricinoleic acid biosynthetic pathway
Cancer pathway gene set targeted only by natural products for a cancer driver target
An overview of proteins and pathways activated and targeted by PemKSa toxin in C
The TGF-β signalling pathway with showing key disease genes, drug targets, and the regulation relationship with FOXN3
Schematic representation of MINA Workflow
A hypothesis working model for Nek2B-mediated chemotheropy-resistant mechanism in TNBC
Proposed mechanism for the inhibitory effects of ASP on the migration, invasion, and angiogenesis of HCC cells
The MC4R signaling pathway plays a vital role in regulating appetite and energy balance
Examples of representations for contextualizing disease associated genes
Analysis of severe asthma differential expression gene signature in the context of STRING protein association network
Significant pathways identified using Tied Diffusion through Interacting Events method, an approach that can extract the most likely set of interconnectors between two sets of nodes
Chronic inflammation activates multiple signaling cascades
A proposed model for the metabolic effects of L-norvaline in the 3√óTg-AD mouse brain.The treatment leads to reduced quantities of Aβ fibrils and prefibrillar oligomers (Aβo), which is caused by a decline in the levels of amyloid precursor protein (APP) but not beta-secretase 1 (BACE-1)
Binding of ANGPT1 to TIE2 induces autophosphorylation of TIE2 and the subsequent activation of multiple downstream pathways involved in migration, inflammation and cell survival
Evaluations on Substrates of FBXL Family E3s(A and B) Known (red edge) and predicted (gray edge) ESIs for FBXLs
Pathogenesis of hRSV and molecules with a biomarker potential induced in the airways during hRSV infection
Exercise-induced myokines mediate organ cross-talk and improve cardiometabolic health
The possible mechanism of CAPE-pNO2 inhibits TNBC growth and metastasis
Schematic representation of proposed MFG-E8 signaling in radial glial cells (RGL) via Œ±vβ3/PI3K/Akt/mTOR pathway
PD-1 signaling pathway in T cells.When engaged with a ligand, PD-1 becomes phosphorylated at its cytoplasmic tyrosine residue, leading to binding of protein tyrosine phosphatases (PTPs), such as SHP2
The underlying mechanism of SSa on T cell-mediated immune surveillance in breast cancer
Mechanistic role of NRP-1 in intrahepatic angiogenesis of liver cirrhosis.A proposed model depicting the role of NRP-1 in intrahepatic angiogenesis of liver cirrhosis
PI3K-AKT-mTOR signaling and Metformin targets
Summary of changes related to insulin-autophagy pathway observed in Parkinson’s Disease
Insulin and autophagy signaling modulation in Huntington’s disease (HD)
Gene network analysis of RNA-Seq data from MDA-MB-231 and OVCAR3 cells
Schematic presentation of the anti-TNBC mechanism of Ilamycin C
Hypothesized therapeutic role of blocking IL6 pathway in Sarcoidosis
. The possible signaling pathways involved in fisetin-induced inhibition of migration and invasion in U-2 OS cells in vitro.
Hydrogen sulfide interaction and effects upon the activity of its biological targets
Integration of photosynthetic light reactions and C metabolism
The mechanism of anti-hOrai1 channel monoclonal antibody (mAb) action on the human T-cell
During isolation, the up-regulation of NPF2 signal suppresses the NOS transcription by inhibiting CREB-B phosphorylation catalyzed by PKA, thus reducing locomotor activity
NanoString mRNA analysis of stem cell-related signaling pathways in miR-25 overexpressing LX-2 cells
β1 integrin induces EGFR- or HER (ErbB2)-targeted therapy resistance
Schematic overview of pathways that are involved in desmoplasia in pancreatic cancer, including drugs and their targets
Working model for the effects of DCA described in this study
Schematic representation of the consequences of tricarboxylic acid (TCA) cycle disruption in pheochromocytomas and paragangliomas (PPGL)
Model of pyCyp protein effects on EGFR signaling in IEC-6 cells
Regulation of YAP/TAZ in epidermal cells
The de novo pyrimidine and purine synthesis pathways
The role of the Hippo pathway in the pathogenesis of tissue fibrosis
Schematic model of regulation of the Hippo pathway by numerous signaling pathways in cancer
YAP/TAZ-mediated regulatory networks in cancer
Downstream effector proteins of the major Rho GTPases, Rac1, Cdc42, and RhoA
RAC1 signaling in tumor cells: RAC1 signaling in tumors cells and the involvement of the RAC1 protein in tumorigenesis and drug-resistance as presented in the review
Signaling Pathways and Cellular Processes Regulated by Keratins, Vimentin, and Nestin
The interconnected pathways of non-essential amino acids (NEAA) metabolism
Flaccidoxide-13-acetate-induced apoptotic pathway in bladder cancer cells
PPAR (peroxisome proliferator-activated receptor) signaling pathway enriched of differentially expressed genes (DEGs) in the jejunum of broiler chickens
A role for fibroblast-derived metabolites in tumor-stroma interactions
Illustration of the main signaling pathways activated upon Ang2 binding to endothelial cells
RKIP protein as a signaling modulator in lung cancer
Schematic view of PKCŒ± inhibitory activity on the Wnt/β-catenin signaling pathway in the normal colon epithelium and in colon cancer
Proposed mechanism between mTOR Signaling Pathway, Inhibitors and Photodynamic Therapy (PDT)
NOX4-related mechanisms in thyroid carcinogenesis
Canonical and alternative Hippo pathways
Roles of the Hippo pathway in effector T cell differentiation
Dual functions of the cancer cell-intrinsic Hippo pathway in immune modulation
DEGs that are located in the neighborhood (putative cis-targets) of DELs and that are associated with Notch signaling pathway and stress granule formation
Pathway visualization using downregulated differentially-expressed unigenes in Axon guidance, Regulation of actin cytoskeleton and Adherens junction
Pathway visualization using downregulated differentially-expressed unigenes in cAMP signaling, Focal adhesion, Calcium signaling, Hippo signaling in fly and Notch signaling
A schematic representation of the proposed mechanisms of IRF5 activation
Cytosolic recognition of foreign nucleic acids and activation of interferon stimulated genes (ISGs)
Interactions between viruses, RNA interference (RNAi), and the interferon pathway in mammals
Upregulated genes in proteasome biosynthetic pathway at 24‚Äâh after inoculation using F
Pathways were constructed in Pathway Studio
Schematic representation of the roles of the cAMP-PKA and cGMP-PKG pathway in DRG neuron hyperexcitability after peripheral injury or injury- related stress including chronic compression of DRG (CCD) and acute dissociation of DRG (ADD)
Hematopoietic cell lineage signaling pathway in the male and female groups
(A) Cytokine-cytokine receptor interaction signaling pathway map in the... (B) Cytokine-cytokine receptor interaction signaling pathway map in the...
Semantic analysis of factors involved in spheroid formation: (A) Protein-protein regulation of follicular thyroid cancer cells exposed to µg; (B) Direct protein interactions; (C) Gene interaction of various differentially regulated genes of thyroid cancer cells exposed to µg conditions
This figure shows the insulin signaling pathway
Mechanisms of TGF-β-mediated skeletal muscle fibrosis
Schematic representation of some of the signaling pathways involved in the differentiation of ADSCs into IPCs
Pathway analysis reveals the dysregulated expression of apoptosis-inducing genes
Cross-talks between tumor and immune cells determining chemo-immune-resistance
Scheme of the mechanisms involved in the rise of blood pressure in low calcium intake by an increase in peripheral vascular resistance
Set of motor neuron proteins in the MAPK signaling pathway
Schematic representation of possible mechanisms releasing mitochondrial components into the circulation
Effects of Butyrate on Mitochondrial Apoptotic Pathway
Effects of Butyrate on Cell Death Pathway
Effects of butyrate on signaling molecules through its receptors
Effect of butyrate on the Wnt signaling pathway Butyrate can increase Wnt1/2/3 expression, which bind to their receptor Fzd to activate Wnt signaling pathway
Effect of butyrate on methylation of oncogene HEY1
Crosstalk of signaling pathways under butyrate influence
Simplified diagram of the signaling assays measured
Schematic representation of leptin-induced signaling pathway
Schematic representation of adiponectin-induced signaling pathway
Gene net correlated to JA, ABA and other hormone biosynthetic, signaling and response pathway under water stress
Tumor-associated macrophage (TAM) function in the ovarian cancer tumor microenvironment (TME) and examples of therapeutic strategies
Schematic representation of the transcriptional regulation and role of CIDE pathway in controlling hepatic lipid metabolism (red and green arrows indicate respectively up- and down- regulated genes) Under HFD–F treatment the gene expression of protein involved in triglycerides synthesis and storage, resulted increased
Known mechanisms and signaling pathways involved in histone deacetylase inhibitor-activated induction or suppression of autophagy
Anti-inflammation mechanisms of molecular hydrogen during sepsis
Anti-apoptosis mechanisms of molecular hydrogen in sepsis
Anti-shock mechanisms of molecular hydrogen during sepsis
Curcumin modulates cancer progression by controlling diverse signal transduction pathways
Construction of a regulatory network for integrated miRNA-target genes
Synthesis and function of NAD+ in the cytoplasm and nucleus
Synthesis, metabolic pathways and function of acetyl-CoA
Synthetic representation of the main mechanisms leading to BRAF and MEK inhibitors acquired resistance frequently present in melanoma and colorectal cancer in vivo and in vitro
Necroptosis signaling pathwayNecroptosis can be caused by a variety of stimuli, including the ligands of the death receptor, TLRs, IFN receptors, and certain pathogens
Transcriptional Regulation of Proteasome Subunit Genes
Top-ranked drug targets are highlighted with blue-border
The Musashi2 (Msi2) gene is a major factor in normal hematopoietic and leukemia stem cells
MiR-503 suppresses cell proliferation and invasion of gastric cancer by targeting HMGA2 and inactivating WNT signaling pathway
(A) The network of RSV-correlated pathways for RNA set1. (B) The network of RSV-correlated pathways for RNA set2. Blue and green...
Possible interactions between ASD causal genes and RA signaling
ASD causal genes affecting BMP signaling and potential crosstalk with other signaling pathways
(a) Model depicting the potential involvement of the Mek/ERK1/2-MAPK and... (b) Simplified schematic showing the major components of the PI3K/Akt/mT...
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of MAGE A9 in patients with esophageal squamous cell carcinoma (ESCC)
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of MAGE A11 in patients with esophageal squamous cell carcinoma (ESCC)
Signaling pathways modulated by EV miRNAs associated with T2DM
The transforming growth factor-β (TGF-β) signaling pathway with marked expression levels of deregulated genes
Hippo Signaling pathway with marked expression levels of deregulated genes
Schematic diagram of enriched integrin signaling pathway in non-type subtype of bladder carcinoma cell lines
Bradykinin effect on TJs: bradykinin (BK), interacting with its receptors B1R and B2R, induces the intracellular release of Ca2+ that can affect occludin polymerization as well as increase the production of nitric oxide that relaxes the junctions
A proposed molecular mechanism of EP that protects the kidney against renal IR injury
PTEN/PI3K/AKT/FOXO3 signaling and pathway modulators
Caveolin-1 upregulates Pofut1 by increasing phosphorylation of CREB, Sp1, HNF4A, and c-Myc via the mitogen-activated protein kinase pathway and activates Notch signaling to enhance invasion and metastasis in mouse hepatocellular carcinoma cells
Possible mechanisms of action of targeted polyIC
Potential mechanism of rapamycin’s anti-angiogenic and anti-lymphangiogenic effects in melanoma
unctions and subsequent pathways of eukaryotic initiation factor 5A2 in human digestive system neoplasms
The mechanistic diagram of NGF and ILM-mediated proliferation promotion by regulating cell cycle of Müller cells
Negative regulators of NRF2 are found in autophagy
Proposed pathway for metabolic detoxication of AAI
Simplified schematic of the PI3K pathway, which highlights the common targets for small molecule inhibitors
Salient features of EBV latent transcripts during B-cell transformation, followed by B-cell lymphoma development
Network diagram displaying the IAV-dependent phosphorylation changes in the actin cytoskeleton and focal adhesion KEGG pathways
Simplified signaling pathway: this simplified signaling cartoon encompasses all significant molecular changes detected in this study in spleen, hippocampus, and plasma after PEA treatment (PEA/sal)
Shown are the edges whose scores exceeded the threshold ; edges are labelled with their scores
. Bile acid synthesis, enterohepatic circulation of bile acids, and bile acid transport.
Canonical activation of HH-GLI signaling
Non-canonical activation of HH-GLI signaling by oncogenic pathways
A schematic diagram illustrate the potential mechanisms of VPA and gemcitabine on pancreatic cancer cells
Schematic shows the regulation of CCK-BR on IA and the involvement of CCK-8/CCK-BR in pain sensitivity
Schematic represents regulatory molecules involved in the ubiquitin-proteasome degradation pathway of BCR-ABL protein
Schematic represents regulatory molecules involved in the ubiquitin-lysosome, autophagy-lysosome and caspase-mediated degradation pathway of BCR-ABL protein
The PI3/AKT/mTOR signaling pathway in tumor cells and regulation by bioactive peptides of the PI3/AKT/mTOR signaling pathway
Functioning of the AMPK signaling pathway in cell metabolism and its regulation by bioactive peptides
The STAT3 signaling pathway and its regulation by bioactive peptides
The TRAIL death receptor pathway and its regulation by bioactive peptides
The signaling mechanism of MUS81 and CyclinB
A schematic diagram of the proposed function of the lncRNA SULT1C2A‐rno‐miR‐466c‐5p‐Foxo4 axis during somitogenesis stage from GDs 9 to 11
The possibly mechanisms underlying dihydromyricetin (DMY) against sodium nitroprusside (SNP) in the HUVECs
Pathway map for “LRRK2 in neurons in Parkinson’s disease”
TGF-β1 ligation of the TGF-β receptor complex leads to a Smad3 dependent increase in ATF4 mRNA abundance as well as mTOR activation
The PI3K/AKT and cell cycle signaling pathway model of NKTCL
Upstream regulatory molecules of Slit/Robo
Roles of Slit/Robo in neurocyte navigation
A model depicting drought tolerance of two sesame genotypes
The summary and schematic diagram of this study
Transcriptional changes of genes involved in fatty acid catabolism, MVA formation, and energy metabolism by ŒîYPL062W, whose reactions mainly occur in the peroxisome (A), cytoplasm (B), and mitochondrion (C), respectively
Photic signaling pathways involving main kinases activities in the circadian clock
Proteolytic processing of APP by non-amyloidogenic pathway and amyloidogenic pathway.In the non-amyloidogenic pathway, APP is sequentially cleaved by Œ±-sec and γ-sec generating sAPPŒ±, p3 and AICD fragments
LRRK2 kinase activity regulates PKA-NFŒ∫B p50 inhibitory pathway.Microglial cells with LRRK2-G2019S exhibit increased LRRK2-RIIβ interaction and RIIβ phosphorylation state and a reduction of PKA-mediated NFŒ∫B p50 phosphorylation level, indicative of an inhibition state of PKA
The molecular mechanism of elicitation: Recognition of elicitors by plasma membrane‐bound receptors results in ion fluxes, Ca2+ burst, cytoplasmic acidification, ROS burst, NADPH oxidase activation, G‐protein activation and mitogen‐activated protein kinase phosphorylation
a Growth factor-induced HIF-1α protein synthesis pathways
During the hypoxic insult, cells release adenosine triphosphate/adenosine diphosphate (ATP/ADP) that accumulate in the extracellular space
Association between miRNAs of interest and their predicted targets in the insulin signaling pathway (A) and Type II diabetes mellitus pathway (B)
Cellular action of FSH and FSHR through the classical cyclic AMP/protein kinase A signalling pathway
Crosstalk between mitochondria and peroxisome: the pathogenic Mtb enters into the macrophage cells via different PRRs like mannose receptor (MRs) or TLRs
Mechanistic interactions between VEGF-targeted anti-angiogenic therapy and checkpoint inhibitors in the systemic treatment of mRCC
Li-ESWT: Low-intensity extracorporeal shock wave therapy; Frizzled: receptor of WNT; BDNF: Brain-derived neurotrophic factor; GSK-3β: Glycogen synthase kinase-3 beta; β-Cat: beta-catenin; PI3K: Phosphoinositide 3-kinase; Akt: Protein kinase B (PKB), also known as Akt; Src: Src is short for sarcoma, a Proto-oncogene tyrosine-protein kinase Src; TSC2: Tuberous Sclerosis Complex 2; GFR: growth factor receptor; RAS: molecules of MAPK/ERK pathway; RAF: molecules of MAPK/ERK pathway; MEK: mitogen-activated protein kinase kinase; mTORC1:mammalian target of rapamycin complex 1; FAK: Focal Adhesion Kinase; VEGF: Vascular Endothelial Growth Factor ; SOS: Son of Sevenless
Simplified Scheme of the Phenylpropanoid-Lignin Biosynthetic Pathway, Illustrating Three P450 Enzyme-Catalyzed Hydroxylation Reactions in Monolignol Biosynthesis.ALDH, aldehyde dehydrogenase; CAD, (hydroxy)cinnamyl alcohol dehydrogenase; CCoAOMT, caffeoyl CoA 3-O-methyltransferase; CCR, cinnamoyl CoA reductase; 4CL, 4-hydroxycinnamoyl CoA ligase; COMT, caffeic acid/5-hydroxyferulic acid 3/5-O-methyltransferase; CSE, caffeoyl shikimate esterase; HCT, hydroxycinnamoyl CoA:shikimate/quinate hydroxycinnamoyltransferase; PAL, phenylalanine ammonia lyase; PTAL, phenylalanine and tyrosine ammonia lyase; SGT, sinapate glucosyltransferase; SMT, sinapoylglucose:malate sinapoyltransferase
T cells are differentiated into multiple T cell subtypes including Th1, Th2, T-fh, Th17 and T-reg cells
Metabolic network of Pseudomonas species
MET protein structure (a) and HGF/MET signaling pathway (b)
Schematic model of CCI in inducing the activation of microglia and NP
HT regulates OS-induced mitochondrial dysfunction and osteoblast apoptosis
Mutations and signaling pathways involved in LMs
Schematic diagram summarizing the possible pathway of key elements in GSD
Proposed model of regulation of endothelial barrier function by FBXW7
A schematic illustration of the interleukin (IL)-12/IL-23 pathway
Pheromone response and negative feedback
Interaction network formed by the encoded proteins of genes showing P values of potential relevance in our study (P < 1 × 10−4), according to the presence/absence of carotid plaques
Dorsal root ganglion (DRG) neurons branch out to the skin with transient receptor potential channel vanilloid 1 (TRPV1)/transient receptor potential channel ankyrin transmembrane protein 1 (TRPA1) and other receptors expressing
Summary. (A) The treatment of HCC cells w... (B) In turn, this leads to the c... (C) We uncovered that Cdk5 inhib... (D) Thereby an inhibition of Cdk...
Three classic signalling pathways were included: (A) Wnt-Ca2+ signalling; (B) β-catenin dependent signalling; (C) PCP signalling
Japanese encephalitis virus (JEV) intracellular effect mechanism
The intensity of the stimulus that induces DNA damage and the degree of activation of PARP1 determines the fate of a cell toward survival or death
(a) Simplified figure depicting the roles of RORC consensus pathway memb... (b) The RORC consensus pathway was validated using STRING protein–protei...
Nuclear gene-encoded regulatory factors are essential for mitochondrial biogenesis and function
Mechanisms promoting regulatory T cell (Treg) development and immunosuppression in the tumor microenvironment
Model of phosphorylation of cofilin and actin cytoskeleton rearrangement induced by gliotoxin during A
Possible underlying mechanism of PAR4 signaling
A schematic presentation of PI3K-Akt intracellular signaling
Integration of TRP channel involvement in mechanotransduction-associated mechanisms during cell migration
The potential mechanisms underlying EOC chemoresistance and the sensitizing effect of PI3K inhibition
Connections between the cAMP/PKA pathway and virulence-related functions in C
Coordinated interactions between glycolysis, citrate cleavage enzyme, and glutaminolysis for the fatty acids biosynthesis in growing tumor cells
Association between high glycolytic flux and extracellular pH (pHe) gradient formation by carbonic anhydrase, as well as proton pump and exchangers
Blue labeling, tumor suppressors and inhibitory signaling; punctate line, negative feedback; red labeling, oncogenic proteins and activating signaling; purple, p85Œ± (PIK3R1) with dual function; green, signaling lipids; bold letters, the proteins mutated in SEGA-like periventricular glioblastoma (NF1, TSC1 and mTOR from this study, and B-Raf from [, ]); underlined, some other mutated proteins contributing to the high grade phenotype; circled, the oncogenic proteins with FDA-approved drug inhibitors; black labeling, cellular effects of the pathways
Schematic diagram of the purinergic signaling complex
In response to ER stress, Bip dissociates from ER stress transducers and binds to unfolded and misfolded proteins, resulting in the activation of ER stress transducers PERK, IRE1 and ATF6
Schematic representation of curcumin mediated inhibition of cell growth via inhibition of AKT signaling and activation of mitochondrial apoptotic pathway
Schematic of T-cell receptor (TCR) signaling
Dual aspects of GM-CSF immunomodulatory effects
Possible pathways underlying the DLL1/Notch signaling pathway defect
A model describing the mechanism regarding the inhibitory effect of IFITM2 on Type I IFN signaling pathway
KEGG enrichment analysis (DAVID) of the genes downregulated upon PAC treatment (fold change < −2 and FDR < 0.05) The model depicts the signaling pathway of multiple plant hormones
Dysregulated immune response in the primary mediastinal B‚Äêcell lymphoma (PMBCL) tumour microenvironment
Endoplasmic reticulum (ER) stress signaling
Nodes represent genes that are either upregulated (red), downregulated (green), or absent from our original differential expression analysis (white), but play an important role in the tumor-specific signaling network according to Ingenuity Pathway Analysis
Schematic of the proposed mechanisms by which norepinephrine (NE) and corticosterone/cortisol (CORT) regulate sterile inflammation
Signaling pathway and inhibitors of inflammasomes
PKM2: Junction of Metabolic Networks and Signal Cascades
AMPK integration of energy stress shapes mTORC1 activity at the lysosome
LINC00520 suppresses EGFR expression and inactivates the PI3K/Akt signaling pathway, thereby suppressing cSCC migration, invasion and metastasis
The major mechanisms regulated by SUMOs and SUMOylation in kidney disease
Surface adhesion molecule ICAM-1 and EPCR are known molecules facilitating binding of PfEMP-1 expressed on iRBCs
Schematic diagram showing the critical role of FDPS in normal prostate and prostate cancer and its associated potential mecahnism (s)
Ang II = angiotensin II; ARB = Ang II type 1 receptor blocker; CYR61 = cysteine-rich angiogenic protein 61; Fima = fimasartan; hCSMC = human coronary artery smooth muscle cell
Illustration depicting primary signalling mechanisms of different neuronal and astrocytic proteins encoded by genes implicated in ID/ASDs
Two regions in the ER are involved in the process described in : activation function 1 (AF1), which is activated by growth factors acting via the mitogen-activated protein kinase [MAPK] pathway, and activation function 2 (AF2), which is activated by estrogen (, )
Immature and mature neutrophils have different metabolic requirements
Essential metabolism and mitochondrial regulation on B cells (A) and Antibody-Secreting Cells (B)
Cooperation of 17-aminogeldanamycin (AG) and trametinib (TRA) or vemurafenib (PLX) a A schematic summary of molecular effects of TRA, and PLX activity, and 17-aminogeldanamycin-mediated HSP90 inhibition in melanoma cells
A variety of seed gene sets were used to test the workflow’s performance
Simplified schematic representation of the affected pathways in an emerging honeybee worker that impact Varroa and DWV symptoms via their interactions
Signaling pathway downstream of TLR4 receptor in platelets with related cellular events and their regulatory miRNAs*
Simplified schematic illustration of pathways for Wnt/β-catenin, ERK/MAPK and PI3K/Akt and PGE2-metabolism
HLA genes HLA-A, HLA-B, and HLA-C encode the MHC class I proteins that present intracellular peptides on the cell surface to T cell receptors (TCRs) and require B2M for stabilization on the cell surface
Ubiquitination-monitored regulation of the Wnt/β-Catenin pathway in colorectal cancer (CRC) cells
(A) Glycolysis/gluconeogenesis pathway. (B) Phenylpropanoid biosynthesis pathway in CD... (C) Phenylpropanoid biosynthesis pathway in TD...
Pathogenic mechanisms of hyperglycemia through the production of AGEs
Role of the RAS and the hexosamine biosynthetic pathways in DCM
The survival signaling pathways related to the PI3K/Akt pathway in mouse macrophages
TGF-β-induced growth inhibition and apoptosis
Targeting the TGF-β signaling pathway in cancer
The process of activation/trans-differentiation of hepatic stellate cells into activated, myofibroblast-like cells (HSC/MFs) as modulated positively (blue arrows) or negatively by mediators released by different hepatic cell populations involved in chronic liver injury
Mitogen-activated protein kinase (MAPK) cascades in activated, myofibroblast-like hepatic stellate cells (HSC/MFs)
Major phenotypic responses in activated, myofibroblast-like cells (HSC/MFs) as well as, more generally, in hepatic MFs
Diagram of the regulation and role of the PI3K-AKT-mTORC1 pathway in ribosome biogenesis and translation initiation
Leptin receptor signaling is mediated by JAK-STAT, PI3K-Akt, and SHP2-ERK pathway
Molecular mechanisms of alcohol-induced apoptosis and autophagy in hepatocytes
The role of extracellular vesicles (EVs) in the motoneuron–muscle communication
Schematic pathway predicting the role of sodium acetate-induced genes in G
Upon T-cell receptor (TCR) signaling, the protein arginine methyltransferase PRMT5 interacts with DUSP14 and induces its methylation on Arg17, Arg38, and Arg45 residues
The agent that activates the cascade in the MAPK pathway, which can lead to TJs opening or assembly
Schematic diagram of the mechanism by which EPD attenuates IMQ-induced psoriasis by inhibiting the inflammation responses via TLR7/8–MyD88–NF-κB–NLRP3 inflammasome signaling pathways
Mitochondria-mediated apoptotic signaling pathway by JNK and p38
Gradient-triggered activation of the cAMP-dependent pathway controls signaling from stimulatory G protein-coupled receptors
Schematic diagram depicting the role of the hepcidin/ferroportin axis in systemic iron homeostasis and local iron homeostasis in PASMCs
Proposed model of OLFM4‐induced STAT3 activation mediated by the LGR5‐Wnt signaling pathway in HCC
KEGG pathways enriched by the differentially expressed mRNAs in the competing endogenous RNA network
Proposed schematic mechanism of EBV-associated gastric carcinogenesis via the activation of the PI3K/AKT/mTOR pathway, and its blockade by CMG002
illustrates the contractive and proliferative role of increased [Ca2+]i in PAH PASMC
Diagram summarizing the role of glia connexin changes in demyelinating disorders
ROS involved in vegetative apical meristem identity in the shoot apical meristem
Outline of the potential mechanism of sEH inhibition-stabilized EETs in blocking NSAID-induced GI ulcers
Outline of potential mechanism of sEH inhibition-stabilized EETs in inhibiting colonic adenoma—carcinoma sequence via targeting inflammation and its activated Wnt/mutant p53 signals
(A) Diagram of ellagic acid target proteins from the DrugBank database. (B) Network of the 17 EA-targeted proteins and their interactions from t...
Pathway schematic of the effect of paeoniflorin on TGF-β1/Smads signaling pathway in chronic heart failure rats
Differentially expressed genes were labeled in the proteoglycans in cancer pathway in the placenta after IVF-ET during the first trimester by KEGG
Fanconi anemia curated map, based in the KEGG FA pathway
Isobutanol biosynthesis pathway in yeast S
Schematic of MUC17 inhibits the progression of human gastric cancer by limiting inflammatory responses
Pathophysiology of autism based on our findings showing the impact of reactive oxygen species (ROS) at different levels of intermediary metabolism and the consequences of brain 5-methyl-tetrahydrofolate (5-methyl THF) deficiency due to FRŒ± autoimmunity
The probable mechanisms of the effects produced by lncRNAs on TBI.Notes: There are several lncRNAs that have been reported to play different roles in the process of TBI
Connection between helper T cell differentiation and HBP
Possible antifibrotic mechanism of exogenous hydrogen sulfide in diabetic cardiomyocytes
Temporal changes in the transcriptome related to the central metabolic pathway in a synchronized C
Chinese herbal medicines inhibit the activation of the HIF-1 pathway in cancer treatment through different targets
Herbal medicines promote the activation of the HIF-1 pathway through different targets in ischemic stroke
Protein-protein interaction network complex and modular analysis
STING pathway activation in DNA repair deficient breast cancer
Snapshot of trastuzumab resistance pathway
Consequence of post-translational modification of viral and host proteins during geminiviral pathogenesis
Implication of various approaches employed by host-mediated resistance factors in defense against geminiviruses
Schematic diagram of E6 mediated activation of STAT3 signalling in HPV+ cervical cancer cells
(A) Acute Myelogenous Leukemia cells (AML) in t... (B) BMP (orange) expression is upregulated in A... (C) EVs isolated from ER-stressed Molm-14 cells...
Overexpression of IFITM3 combined with Smad4 promoted Smad2/3 phosphorylation, thereby affecting transcriptional regulation to induce PTHrP-driven bone metastasis
Suppressive mechanism of regulatory T (Treg) cells
Possible mechanism of matrine on inhibiting skeletal muscle atrophy
The metabolic pathway of glycerophospholipid, glycolysis, and TCA cycle of S
Model illustrating potential effects of cold stress on membrane lipid pathway in peanut
Release of mitochondrial proteins and mtDNA initiates an inflammatory response in CICD
Mechanisms by which bacteria influence cancer development and progression
The schematic summary of molecular pathways induced by HBx-B genes
A Diagrammatic Sketch of miR-26a-5p-Mediated Osteoblast DifferentiationmiR-26a-5p is upregulated in bone and reduces PTEN translation, thereby activating the PI3K-AKT signaling pathway, subsequently inducing RunX2 expression and increasing bone formation
The HBP regulates multiple proteins in cancer cells via OGT
The anti-pancreatic cancer pathway of Wumei Pill
Cancer predisposing risk factors are known to cause cellular injury, which in turn activates normal inflammatory response
Differentially expressed genes obtained by RNA-seq in the ERG-inducible LnTE3 cells were analyzed using IPA
The hypothesis of the mechanism of IDH mutant gliomas
Pathway map based on renal age-associated gene (RAAGs).Enriched molecular pathways based on the set of 634 RAAGs are displayed
The mechanisms of ionizing radiation sensitizing and resistant effects in various subtypes of breast cancer and irradiation-induced apoptosis
POL-P3b-induced protection against tumor-induced intestinal DC apoptosis through the cross talk between TLR4/PI3K/AKT and NF-Œ∫B signaling pathway
CK2 actions on chaperone machinery (a), NF-Œ∫B signaling (b), and PI3K/AKT/PTEN pathway (c)
Intestinal disease-related pathway including MAPK signaling pathway, NF-kappa B signaling pathway, calcium signaling pathway, and chemokine signaling pathway
TLR4-mediated inflammatory signaling pathway in the rumen epithelium
Differentially expressed genes in p53 signaling pathway
a: Simplified rationale for performing studies in NHP sepsis models of antibody inhibition of TNF-α and IL-6
Therapeutic strategies targeting NAMPT against stroke
a Ceramide-induced axon loss and neuronal apoptosis
Antioxidant mechanism of the NRF2 pathway
Signaling pathways involved in Œ±-CGRP-induced vasodilation
Differentially expressed miRNAs in thyroid cancer tissues modulating the MAPK pathway
Differentially expressed miRNAs in thyroid cancer tissues modulating the PI3K pathway
Signaling crosstalk at receptors and adaptors
Pathway-based analysis for glycolysis, TCA cycle and pentose phosphate pathway
Schematic diagram of the relationships among Gal-1, MAPK JNK/p38 signalling pathway and EMT
Pathway Map of Glioblastoma obtained from Wikipathways using Cytoscape
NRF2 acts as a central hub to facilitate the transition of BCSCs from the M to E state as well as the maintenance/proliferation of E-BCSCs under metabolic/oxidant stress
Molecular regulators and signalling mechanisms involved in the activation of astrocytes
Schematic diagram of the molecular mechanism underlying the promoting roles of the expression of CSE on the progression of breast cancer
A proposed mechanism of the p75NTR as a mediator of synaptic changes during SD
Main energy metabolism and carbon/nitrogen fluxes in heterocysts
Long non-coding RNA acting within the NODAL signalling pathway
Signaling pathways involved in the protective effects of tea bioactive compounds against cardiovascular diseases
Expressional change of genes for the central carbon metabolic network in Kmmig1
Lipotoxicity of VLDLs on mediating maladaptation of calcium regulation to derangement of sarcomere proteins in atrial myopathy
Distinct molecular and morphologic features of apoptotic, necroptotic, and necrotic cell death
Role of inositol in insulin signalling pathway (inspired on Larner and Brautigan)
Schematic outline of the salinity-induced response pathway based on proteome, gene expression, and physiological changes in chickpea leaves
Pathway of the EGFR-IGF1R model in lung cancer []
Overview of macrophage metabolic pathways
Tumorigenic mechanisms of Fusobacterium nucleatum in colorectal cancer
(A) Slit2/Robo4 signaling inactiva... (B) Robo1 and Robo4 competitively... (C) Slit2 binds to the Robo1-Robo4... (D) Robo4 transduces inhibitory Sl...
miR-613 overexpression and FN1 silencing inactivated the AKT signaling pathway to inhibit invasion, migration, and angiogenesis in NPC, corresponding to down-regulated Bcl-2, MMP-2, MMP-9, VEGF, and CD31 as well as decreased the ratio of Bcl-2/Bax and increased expression of Cleaved-caspase3
Platelets involvement in the pathogenesis of AAVs
Conceptual model of cellular processes within Tv
Overview of the ubiquitin regulations on mTOR signaling components
Schematic drawing to illustrate JAK-STAT signaling pathway
Schematic highlighting the signaling cascades that are dependent on erbB4 in MPNSTs
Risk pathway interaction network from iDRW(GP) and iDRW(GMP)
Canonical pathways generated in Ingenuity Pathway Analysis of interferon signaling pathway of DEGs in (A) T helper cells, (B) T cytotoxic cells, (C) monocytes, and (D) B lymphocytes of infected goats at 9 dpi
Canonical pathways generated in Ingenuity Pathway Analysis of Oncostatin M signaling pathway of DEGs in (A) T helper cells, (B) T cytotoxic cells, (C) monocytes, and (D) B lymphocytes of infected goats at 9 dpi
TSL suppresses angiogenesis by inhibiting the VEGFR2 signaling pathway
Showing Possible effect of the mutation in leptin–leptin receptor signaling pathway
Role of the cAMP/CREB pathway in intrinsic apoptosis
The role of CaMKK2 and advanced glycation endproducts (AGEs) within the bone microenvironment
A schematic model showing that LUCAT1 regulates breast cancer stemness by competitively binding to miR-5582-3p and TCF7L2 and consequently regulates the Wnt/β-catenin signaling pathway
Convergent inflammatory signaling through NF-Œ∫B potentiates BRD4-dependent transcription of VI mediators, a result suppressed by apabetalone
Proposed model illustrating the anti-IL-1β activity of matrine
Aberrant activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma
Viral appropriation of cellular nucleocytoplasmic transport
Involvement of FGFR4-related signaling pathways
Ingenuity Pathway Analysis indicates the relation between genes differentially expressed between imatinib-naïve (IM-n) and imatinib-resistant (IM-r) gastrointestinal stromal tumor (GIST) samples
Ingenuity Pathway Analysis integrating differentially expressed genes and microRNAs between imatinib-naïve (IM-n) and imatinib-resistant (IM-r) gastrointestinal stromal tumor (GIST) samples
Synthetic lethality of PARP-inhibitors in HR-deficient tumors
Epidermal Growth Factor Receptor-dependent activation of the MAPK signaling pathway
Potential mechanisms underlying the anti-inflammatory effects of oxytocin (OT) on lipopolysaccharide (LPS)-stimulated microglia
Scheme of copper and silver distribution in a mammalian cell
Interactions between RHOB and EGFR, Ras, PI3K/Akt/mTOR, MYC, and HDAC
Proposed mechanisms for fucoidan-mediated inhibition of osteoclastogenesis
Diagram showing the different molecular mechanisms of canonical nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome activation
Diagram showing the different molecular mechanisms of non-canonical NLRP3 inflammasome activations
Predicted/established targets of selective flavonoids in platelets: Flavonoids modulate platelet activation through multiple mechanisms
Schematic representation of the interaction between Sildenafil, Leucine, PDE2, and PDE3
Simplified scheme of the PI3K/Akt signaling pathway
Janus kinase (JAK)/signal transducer and activators of transcription (STAT) pathway of cytokine action
Network of the sperm proteins differentially associated with male age
mTOR signaling in spermatozoa from older men
Signaling pathways and receptors involved in uveal melanoma (UM) and cutaneous melanoma (CM)
Scheme of BLT2-dependent lipopolysaccharide/Toll-like receptors 4 (LPS/TLR4), interleukin (IL)-33/ST2, or allergen/ high-affinity IgE receptor (FcŒµRI) immune response signaling pathways responsible for IL-13 synthesis in mast cells, contributing to the allergic airway inflammation
A graphical illustration of the proposed mode of FBXW5-induced regulation of intracellular signaling in gastric cancer
(A) Demonstrates a simplified pathway of sphingolipids (SLs) together wi... (B) Demonstrates a simplified pathways of de-novo synthesis of fatty aci...
The TLR2 signal pathway involved in oxidative stress [,]
TLR4 signal pathway in oxidative stress [,]
The schematic representation of physiological and pathological aspects (major sources of oxidative stress) in Alzheimer’s disease (AD) and their corresponding antioxidant defense approach by anthocyanin in cholinergic neurons
Fibroblast growth factor receptors (FGFRs) are highly conserved transmembrane receptors consisting of three extracellular immunoglobulin-like (Ig-like) domains, a transmembrane helical region, and a cytoplasmic region with kinase activity
Biofunction analysis of differentially expressed genes from eWAT (A) Biofunction-overlay of the disease and function related to lipolysis in eWAT; (B) the disease and function in response to CLE in eWAT
A schematic illustration of the effects of SSE on insulin signaling and the suggested mechanism
Overview of the canonical Wnt signaling pathway illustrating therapeutic intervention points targeted by Wnt modulators
Schematic representation of members of the human epidermal growth factor receptor (HER) family, their natural ligands, interaction with the HER2-targeted therapies trastuzumab, pertuzumab, trastuzumab emtansine (T-DM1), lapatinib, and neratinib, and the downstream consequences of these interactions
An overview of proven and hypothetical oxidative stress signaling pathways, where PP2A is involved
The synthesis of BDNF and potential downstream involved in the effects of botanicals and active components on depression
A proposed model of gga- miR-1306-5p regulation on activation of pro-inflammatory responses via targeting Tollip in chickens (Red arrow: up-regulation or down-regulation)
Merged network combining major signaling networks related to the metabolites differentially expressed in the Ingenuity Pathways Analysis.Note: For clarity, proteins and metabolites were merged with different geometric shapes in the relevant network in the hippocampus
Molecular mechanisms of the cGAS/STING pathway as a senescence-associated DNA damage sensor and inflammation trigger
EGFR, MET and NOTCH alterations promotes proliferation, migration and cellular survival via signalling through the RAS/RAF/ERK, PI3K and JAK/STAT pathways, all of which are regularly dysregulated in HNSCC
HPV oncogenesis occurs mainly in the tonsillar crypt epithelium of the oropharynx
Overview of maize metabolic responses to Ustilago maydis infection in specific cell-types
Effects of air pollution and ultraviolet radiation (UVR) on the skin
Signaling pathways underlying the potential involvement of latrophilins in growth cone and actin structures formation
Schematic representation of apoptotic events
Illustration of how SerB2 can be secreted within macrophage cytosol to disturb immune response and cause cytoskeletal remodeling (adapted from [])
Expression of MALAT1 is increased in response to inflammatory stimuli in CD11c+ cells of tolerized allograft cardiac tissue
Herpesviruses modulate the JAK-STAT pathway
The Wnt and R-spondin signaling pathway: In the absence of R-spondin (-Rspo), the membrane ubiquitinase zinc and ring finger 3/ ring finger 43 (ZNRF3/RNF43) associates with the Wnt receptor complex Frizzled/ Low-density lipoprotein receptor-related protein 5/6 (Fzd/LRP5/6), inducing its internalization and preventing its Wnt dependent phosphorylation, thereby inhibiting the downstream Wnt signaling cascade
Signaling pathway nodes effected by loss of CDK11 in A375 melanoma cells following PanCancer Reactome pathways analysis
Effects of SAM on signal transduction pathways
Schematic showing that exosomes carrying miRNAs promote NDV infection
In the absence of Hh signal, Patched1 (Ptch1) inhibits the Hh pathway through the modulation of the Smoothened (Smo)
COPD pathogenesis based on metabolomic analysis
Iatrogenic interference with the initiation of antifungal immunity
Schematic diagram of LPS-mediated platelet activation and TLR4 expression in canine platelets
Modulating PI3K-Akt signaling pathway of SCD
Genes were clustered in the PPI network according to string database (genes from top 10 predicted pathways in BQG-treated group versus BLM group)
Schematic illustration of potential signaling pathways
Scheme of proposed molecular mechanism of Ezrin-induced pancreatic cancer cell proliferation, invasion, and EMT progression.Abbreviation: EMT, epithelial–mesenchymal transition
Mechanisms of Rb pathway loss and assays for their detection
Targeting pathways and molecules in the treatment of NMSC
Activation modes of the NLRP3 inflammasome and the regulatory mechanism of CVDs
Enriched KEGG pathways generated by ClueGO and Cluepedia
The network of Wnt signaling regulates tumor metabolism reprogramming
Schematic model of the E2 intracellular activated pathway impacting on NGB expression levels/intracellular localization and the related antiapoptotic role of both mitochondrial NGB and AKT which appears to be double linked with NGB function
(a) Schematic model of ROS-activated signaling involved in the rapid mod... (b) Schematic model of the E2 intracellular-activated pathway impacting...
Proposed model for the impact of targeted therapeutics, vemurafenib (PLX) and trametinib (TRA) on differentiated/pigmented phenotype of melanoma cells
KXS ameliorated behavioral and pathological deterioration via the improvement of neurotransmitters and PI3K/Akt signaling pathways on the AD model
Schematic diagram showing the proposed signalling pathways for inflammatory and autoimmunity‐associated gene expression via Ca2+ and Ca2+‐dependent/‐binding proteins
Model of innate immune response activation in BRCA2-deficient cells
The TGF-β/Smad signaling pathway regulates spermatogenesis via controlling AJ, TJ dynamics, and Sertoli cell proliferation (green)
Members of TGF-β family activate the pathway via binding to TGFβRII and recruiting TGFβRI
AMPK is sensitively stimulated by the rise of intracellular AMP: ATP ratio, while phosphorylation induced by upstream AMPK kinases (i.e., liver kinase B1 [LKB1] and CaMKKB) and AMP binding will also stimulate AMPK.
MAPKs consist of JNKs, ERKs, and p38 MAPKs
Cellular and molecular responses to extracellular and intracellular DNA
The synthetic metabolic pathway for isobutanol production in E
Interaction network of proteins underexpressed in in vitro matured cumulus complexes (interaction confidence: high (> 0.7), database matches n = 82)
Interaction network of proteins overexpressed in in vitro matured cumulus complexes (interaction confidence: high (> 0.7), database matches n = 116)
Breast cancer cell-based pathobiochemical pathways showing LPHN-induced activation of PKCŒ±, which triggers the translocation of Tim-3 and galectin-9 onto the cell surface which is required for immune escape
Cell signalling events that mediate the switch between self-renewal and differentiation in mouse embryonic stem cells
Model of L-proline-mediated differentiation of mESCs to EPL cells
Hypoxia can induce the apoptosis of proximal tubular cells by increasing oxidative stress driven by TGF-β/Smad signaling-mediated Nox4 expression
Summary scheme represents the possible pathways of drug sensitive and drug resistance to cordycepin in MA‚Äê10 mouse Leydig tumor cells
The conceivable migration pathway related to PNETs based on literatures
READ pathways (p53 signaling pathway, intestinal immune network for IgA production, and colorectal cancer pathway) enriched in DEmRNAs during READ
Cellular glycolysis and oxidative phosphorylation
NF-Œ∫B signaling pathway constitutes a family of transcription factors that are stimulated by pro-inflammatory cytokines or ligands
An example of autocrine and paracrine interactions between NPY neuron (blue) and POMC neuron (green) in the ARC and their downstream effector neuron (i.e., neuron in PVN; beige)
Proposed model of MEK as a key regulatory pathway of the IFN response against RV and RSV in airway epithelial cells
Compound 19 concurrently inhibits STAT3 and NF-Œ∫B transcription factors in colorectal cancer
Schematic representation of the complement system, showing approximately 50 directly involved soluble and membrane-bound complement proteins
LAIR1 signalling pathway in malaria.The LAIR1 pathway is activated by attachment of collagen and collagenous ligands (C1q) to LAIR1 extracellular surface
Ovarian cancer stem cells and macrophages reciprocally interact through the Wnt pathway to promote a pro-tumoral microenvironment
Recapitulative diagram of IL-15 pathway involved in TGF-β signaling
Relation graph of KEGG pathways in which differentially expressed genes were significantly enriched
Schematic diagram summarizing the anti-NSCLC action of butein via activation of ER stress and ROS generation
Schematic diagrams of the CWI pathway (A) and the HOG pathway (B) in S. cerevisiae.
The ETC and ATP synthase are required for normal eye development
Partial diagram of the “Signaling by SCF-KIT” pathway showing the feedback loop that generates the “p-STAT dimers” complex annotated in Reactome
Eight CaWRKY genes (CaWRKY25/28/45, CaWRKY41/48 and CaWRKY33/38/47) are included
(a) Glutamatergic synapse (path:hsa04724) pathw... (b) Sub-network of mGluRs and their regulatory... (c) The interaction analysis of the mGluRs and...
Hcy exposure causes the inactivation of mTOR, potentially through the ERK and PI3K-AKT signaling pathway, which subsequently leads to autophagy activation
Illustration of the anti-fibrotic effects and their relationship between TAF and NS5ATP9 in BLM-induced pulmonary fibrosis
Schematic presentation depicting the signaling connections through which AMPK signaling controls the major activation pathways of MDSCs
Schematic presentation depicting the energy metabolic pathways through which AMPK controls the activation of MDSCs
Curcumin actions on the WNT pathway in cancer therapy
The tumor microenvironment influences the metabolic status of cancer cells with consequences for their metastatic potential
Osteopontin (OPN)-induced β1-integrin activation and HIV-1 envelope signaling converge on mTORC1/2 pathways in a mechanism that promotes neurite outgrowth
. Synthetic Pathway for the Preparation of the Pechmann Scaffold.
A. A diagram of PI3K/AKT pathway, with PIK3CA, PTEN, PIK3R1 and AKT1 as key signaling proteins in the pathway.
Model of AnvM-mediated regulation and its interaction with host cell
Proposed molecular mechanisms underlying the inhibitory effect of NAB on the LPS-activated RAW264.7 macrophages
Network analysis of the differentially expressed proteins between the Dex-treated and control rats identified by the IPA (ingenuity pathway analysis)
The “circadian rhythm-plant” pathway enriched by KEGG analysis of DE mRNA corresponding genes in the cultivar “Huoche” under heat stress
The “photosynthesis” pathway enriched by KEGG analysis of DE mRNA corresponding genes in the cultivar “Huoche” under heat stress
Summary of epigenetic and gene expression differences in the insulin and PI signaling pathways
Schematization of signal transmission and transduction in plant cells
Potential activity pathways for apoptosis induction resulting from cereal phenolic compound exposure (↓ downregulation, ↑ upregulation, Caspase (Cas), pro-apoptotic protein (Pro-AP), anti-apoptotic protein (anti-AP))
Possible mode of cell death pathway in Caco-2 cells
Mechanism of Activation for the Non-Canonical and Alternative NLRP3 Inflammasome Pathways
Mutual interactions of expression of the genes examined with qPCR and shown in ,  and
Schematic illustration of G protein-coupled receptor (GPCR) signaling
Proposed antipsychotic actions to confer bias of GPCR signaling
Potential therapeutic benefits of Selective D2R-β-arrestin2 ligands in prefrontal cortex and basal ganglia in schizophrenia
Signaling pathways selected for the evaluation of the biological effects of essential oils
Representation of S100B effects on Caco-2 cells
Overview of intracellular vesicular trafficking-cellular organelle rough endoplasmic reticulum (RER) Coat protein I and Coat protein II form vesicles that mediate cargo transport between Golgi to ER and ER to Golgi, respectively
RIG-I/MDA5 signaling pathway RIG-I and MDA5 are first activated by recognition of PAMP dsRNA, which causes them to interact with MAVS
Stimulation of TLRs activates multiple signaling pathways
Strategies to inhibit insulin induced PCa invasion and plasticity
The SakA and MpkC SAPK pathway in Aspergillus fumigatus
The mechanism of the loss of cell polarity in CBDL rat lung
Schematic figure illustrating the signalling pathway activation with mechanical ventilation and endotoxaemia
Six main metabolic pathways relevant for immune cell function
Significant dysregulation of genes involved in Colorectal Cancer Signaling Pathway in urothelial cells
Significant dysregulation of P53 pathway in urothelial cells exposed to either S
Schematic representation of the role of p38 mitogen-activated protein kinase (MAPK) in host cell death
Summary of the neuroprotective action of resveratrol
Contrast inflammatory signals in human gingival fibroblasts triggered by the different acylation structures of P
Antibactericidal mechanisms of C5a-TLR2 cross-talk induced by P
Prediction of the target associations of the circRNA-microRNA-mRNA network
(A) Pathway analysis for hyperoxia-responsive g... (B) In Nrf2−/− mice that received PBS, O2 alter... (C) Nrf2-dependently modulated genes during hyp...
Dietary sulforaphane is known to stabilize cytoplasmic Nrf2 through Keap1 binding to inhibit Nrf2 ubiquitination for its proteasomal degradation
Synergistic effect of three combined strategies by targeting complement/C3aR /C5aR1/IL-10 pathway and other treatment modalities
An illustration shows the general process for creating single cell and multi-cell computational models that were validated directly by comparing the predicted results against the chemokine and cytokine profiles produced from the same cells grown in single cell and multi-cell cultures
A schematic representation of a modeled signaling pathway using a G Protein Coupled Receptor activation as an example
The interferon-gamma (IFNG) pathway and its modeled representation to demonstrate the step-by-step calculations for protein-protein interactions at each node in this pathway and as an annexure section of other pathways
Functional enrichment analysis of the 2,397 intersected differential genes
Genetic risk factors and synapse dysfunction in AD pathogenesis
A signaling map and mechanistic map of the Sfrp5/Wnt signaling pathway in ASCVD
Autosomal dominant polycystic kidney disease (ADPKD) is associated with mutations in one of two genes, PKD1 or PKD2, which encode polycystin-1 (PC1) and PC2, respectively
Liver disease in autosomal recessive polycystic kidney disease (ARPKD), which is caused by mutations in the PKHD1 gene (encoding fibrocystin (FPC)), is characterized by cystic dysgenesis of the intrahepatic bile ducts that retain an immature phenotype reminiscent of the embryonic biliary structures (ductal plate malformations)
The upregulation of CCN2 are closely related to oxaliplatin treatment in HCC, and CCN2 interacting with many cell membrane receptors such as LRP6, Met, integrins, etc., significantly enhanced oxaliplatin resistance by activating the MAPK/Id-1 signaling pathway
Schematic Diagram Showing that NXA3 Is Involved in the Progression of IA through the JNK Signaling Pathway
Mechanisms involved in the regulation of glycometabolism in T2DM by RC
(a) Schematic of TriPOINT. Differential gene expression, pathways from G... (b) Sub-graph of the Signaling pathways regulating pluripotency of stem...
The PPAR signaling pathway and DEGs.Abbreviation: DEGs, differentially expressed genes
Signaling cascade in RANKL-RANK induced osteoclastogenesis: A model of IRF8-mediated regulation of osteoclast differentiation
Proposed model to explain how COX-2 might be essential in the stimulatory pathway for ROS production and increased expression of profibrotic genes mediated by PRR activation
Hypothetical scenarios for the role of NGF after systemic oxidative stress
The intrinsic pathway refers to mainly mitochondrial-mediated apoptotic pathway
Proposed molecular mechanisms of PAX3 in glioma pathogenesis and progression
The diagrammatic representation of human hedgehog signaling pathway
Network visualization of the calcium signaling pathway with expression and GWAS information
Proposed model of the Lgr5-mediated stimulation of cancer growth through activation of the Wnt/β-catenin signaling pathway
Predicted mechanisms of ELF1 regulation of doxorubicin-induced apoptosis
a, Comparison of AUC test (two-sided) performance with LR analysis with the time covariate
Graph representation of the Signaling by NOTCH2 pathway as extracted from the Reactome database
Overview of direct and indirect pro-allergenic immune responses to anti-ulcer drugs (AUD)
Novel concepts of tumor microenvironment-targeted therapies or immunotherapies (1) Tumor-associated macrophages/microglia (TAMs) represent a highly abundant cell type in BrM with known roles in mediating tumor cell BBB transmigration and tumor-supportive functions that foster metastatic outgrowth
Changes in expression of genes involved in ethanol oxidation and TCA cycle in K
Pivotal functions of the molecules in heme metabolic pathway in inflammation
Integrin Œ±vβ3 mediates intercellular adhesion in MCAs of GC cells to form an independent functional unit and activates GLI1 through the non-classic ERK1/2 pathway and crosstalk with the classic Hedgehog pathway to maintain cancer stem cell-like phenotype
Schematic representation of NK cell transduction pathways involved in primary immunodeficiencies
Summary diagram of signaling pathway of this study
Schematic diagram showing the activation of Ca2+ signal transduction pathway and other miscellaneous pathways in response to the electrical and mechanical stimulations
Schematic diagram of the intracellular signaling mechanism after sequential treatment with gliotoxin followed by paclitaxel in human ovarian cancer cells
Sirtuins and epigenetic regulation of immune cell functions
Schematic representation of various molecular inhibitors and stimulators in mTOR signalling pathway
Cell signalling dysfunction in mTOR signalling pathway leading to syndromic and idiopathic autism
Pterostilbene (PTS) prevented ROS formation and reversed palmitic acid (PA) mediated increase in hepatic glucose production by reducing expression of genes coding for gluconeogenic enzymes and their transcription factors
The proposed mechanism of apoptosis induction by 3-cloroplumbagin (ChPL) in breast cancer cells
RNA MODOMICS and heterogeneity of tumors
Graphical summary of the anticancer mechanisms of formononetin
Putative Cripto-1 targets the MAPK, FA and ErbB signalling pathways
DEGs in kernels at the 5DAP stage involved in plant hormone signaling pathways
DEGs in the ear leaf (drought/normal) at the 5DAP stage involved in the plant hormone signaling pathway summary of the maize plant response drought stress
Indirect pathway striatal spiny module.The medium spiny neuron dendritic spine, the glutamatergic terminal and the dopaminergic terminal constitute the so-called striatal spiny module (SSM)
Putative actions responsible for the beneficial effects of glucagon like peptide 2 (GLP-2) in the neurodegeneration.Exogenous GLP-2 is able to reduce the expression of markers of inflammation and stress, the glia activation and the apoptosis in the brains of high fat diet mice
A model of the inhibitory effect of Gal-3BP on TAK1-dependent NF-Œ∫B signaling pathway
Representation of the two serrated pathways
Mechanisms responsible for ETR (endocrine therapy resistance) progression
Compounds that inhibit and activate autophagy
Model of miR-146b-3p mediated regulatory mechanism in myoblast proliferation, differentiation, and apoptosis
Schematic drawing of the proposed role of FGFR2c and its signaling in the regulation of autophagy and EMT interplay
Overview of the role of the canonical Wnt/β-catenin pathway in cancer metabolism
Simplified pathways showing the effect of F-6 cell proliferation and death
NMP induced apoptosis in NSCLC cells by dual pathways
Activation of c-Rel signaling by the canonical NF-Œ∫B pathway in B cells
The schematic diagram represents the mechanism of melatonin neuroprotection in mouse brains following traumatic brain injury (TBI)
Unigenes involved in the Wnt signaling pathway: Red and green represent upregulated and downregulated genes, respectively
Molecular mechanism of soft-jet plasma-induced cancer cell apoptosis via the mitochondrial intrinsic pathway and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) activation []
Illustration of proposed mechanisms of stem cell therapy in rescuing ischemia-reperfusion induced acute kidney injury
Rac1 activation is regulated by GEFs and GAP
The mechanism by which alantolactone (Ala) suppresses neuroinflammation
RANKL/RANK signaling pathway from stromal cells/OBs showing downward signaling molecules to the transcription factors in the nucleus that regulate OC differentiation
Stearoyl-CoA desaturase 1 (SCD1) as a molecular target for anticancer therapy
Schematic model of the anti-neuroinflammatory modulation afforded by bakuchiol in activated microglia
CSCs-activated signaling pathways: Schematic representation of the signaling pathway responsible for induction and maintenance of CSC state
Immunosuppressive role of tumour-associated macrophages (TAMs)
Protein network analysis of the overexpressed genes in the TLR non-responsive patient cells
Altered metabolism as the source of nadph biosynthesis
(A) miR526b and miR655 overexpressing cells showing significant down reg... (B) The proposed pathway of tumour associated angiogenesis and lymphangi...
Beneficial role of NSAIDs in cancer process
DNA virus stimulation of the mitogen-activated protein kinase extracellular signal-regulated kinase (MAPK-ERK) cascade
WNT pathway molecules and their involvement in chemoresistance in NB
Schematic illustration of the PI3K/AKT/mTOR/NFŒ∫B Pathway
Summary of Olea europaea extract and its active compounds’ mechanism of action on signaling pathway of EMT
Wnt-EarlyEx tumors show expression of Wnt-associated pathway signatures
Schematic illustration of the role of inflammasomes in lupus nephritis
Oleuropein induces apoptosis in NSCLC A549 cells through mitochondrial glyoxalase 2 (Glo2)
The regulation of genes and myomiRs expression in the IGF/PI3K/Akt signaling pathway during myogenesis
The metabolic pathway designed for improving the titre of γ‐PGA and key metabolic engineering strategies in B. amyloliquefaciens  LL3Δupp strain
Diagrammatic summary of dinoflagellate orthologues predicted in the base excision repair pathway
Diagrammatic summary of the dinoflagellate orthologues predicted in the nucleotide excision repair pathway
Diagrammatic summary of the dinoflagellate orthologues predicted in the DNA mismatch repair pathway
Schematic representation of the action of dietary polysaccharides on the insulin signaling pathway
Model of the (a) glycolysis and (b) PKA-AMPK pathway genes and metabolites modulated by dietary BRBs during oral carcinogenesis
Molecular mechanism by which RV hypertrophy (RVH) develops in response to pressure overload
Functional networks overrepresented in the list of DE mRNA in response to infection of bMDMs with Streptococcus agalactiae strain ST103 compared to uninfected controls
The signal pathway simulation of OPG regulating proliferation and migration of endothelial progenitor cells
JH pathway of S. aquatilis was reconstructed by mapping the annotated proteins to KEGG pathway.
The pharmacokinetic and pharmacodynamics pathways for mycophenolate mofetil
A schematic mechanism of apoptosis in ovarian cancer and some current targeted molecular therapeutic approaches
KLF5-targeted genes in the pancreatic cancer pathway
The molecular consequences of the PrPC/Aβ interaction in AD
Schematic representation of ErbB/PI3K pathway regulation by miR-326
Key events during the development of epithelial-to-mesenchymal transition (EMT) and target pathways for therapeutic use of natural plant compounds (NPCs)
LncRNAs regulate angiogenesis through modulating multiple signaling pathways
Representation of the various selenium metabolic pathways leading to selenoprotein synthesis
The cyclin D1-CDK4/6-RB pathway and crosstalk in breast cancer
A mechanism map depicting the molecular mechanism of BMP2 in HCC
Model of the mechanism of Notch1 signaling and CXCL12/CXCR4 axis in GICs self-renewal, invasion and tumor growth
Comparison of the shrimp IMD pathways (A) and Drosophila IMD pathways (B) and Human TNFR signaling (C)
Interplay between shrimp NF-Œ∫B pathways and WSSV
A schematic model of Dex-SPIONs protect HUVECs from H2O2 damage via inducing autophagy response
Schematical illustration showing the possible molecular mechanism for enhanced osteogenesis by HA-Au nanoparticles by activation of Wnt/β-catenin signaling pathway as well as internalization into the hMSCs.Abbreviations: HA-Au, gold nanoparticles-loaded hydroxyapatite; hMSCs, human bone marrow-derived mesenchymal stem cells
(A) Fourteen signaling (left) and six groups of metabolic pathways (righ... (B) Conversion of interconnecting paths into network representation.
According to the data shown in this report, Hic-5 can be induced by ROS-JNK pathway and transactivated by c-jun and AP4 which may in turn interact with Rac1 and Traf4, and Pyk2 triggering activation of NADPH oxidase, ROS generation and JNK phosphorylation thus sustaining the signal transduction
Translational challenges with systemic and local cell delivery
A graphic representation illustrates how Kaposi sarcoma herpesvirus (KSHV) representative viral proteins (in orange) modulate host cellular signalling proteins (in blue) to promote cellular survival and the inhibition of apoptosis
Kaposi sarcoma herpesvirus (KSHV) encodes an arsenal of viral proteins that modulate multiple innate immune pathways
Schematic representation of extrinsic apoptotic pathway and HPV E6 blockade of FADD mediated apoptosis
Molecular characterization of subpathway signatures
Dysfunctions in canonical Wnt-Signaling contribute to the neuropathology of Alzheimer disease (AD)
Multi-loop model of AD: an integrated perspective on the Wnt/GSK3β, Œ±-synuclein, and type 3 diabetes hypotheses
lncRNAs mediate drug and radiation resistance
Schematic model of the involvement of KRAS in cell survival and growth as well as in tumor microenvironment through MEK‚ÜíERK and PI3K signaling pathways
Diagrammatic sketch of the working hypothesis
Hypothetical scheme of the kefir peptides regulatory pathway
The level of CXCL1 and CXCL2 was very low under normal physiological conditions, but the level was greatly increased under tumor conditions
Natriuretic peptide signaling in adipose tissue
Model of the TORC1–PKA signaling circuit
The IRE1Œ±-XBP1 pathway of the UPR in CF
Biosynthetic pathways for phosphatidic acid production
The key intrinsic immune evasion mechanisms exploited by HPV oncoproteins in keratinocytes (KCs)
Schematic of a proposed model of tau hyperphosphorylation under the conditions of normal and impaired insulin signaling
Dropwort extract exerts broad anticancer effects on MPM cells affecting cell proliferation, viability, migration, metabolism and in vivo tumor growth of MPM cell lines
. Anti-apoptotic pathway of vaspin in vascular cells.
. Summary of citronellol-induced necroptosis and ROS accumulation in human lung cancer NCI-H1299 cells.
Differential pathway regulation in advanced idiopathic pulmonary fibrosis (IPF) lung
The role of autophagy in the differentiation/function of osteoclast, osteoblast and osteocyte
Induced glutathione and reduced beta-alanine metabolism during IS sensing and signaling in response to oxidative stress
The PDAC TME is characterized by dense desmoplastic stroma and resultant hypoxia, which also drives angiogenesis, immune suppression, and numerous signaling events that promote cancer progression, metastasis, and poor patient survival.– The influence of hypoxia on stromal composition and secreted extracellular protein such as lumican is not clearly understood
Drug screening of the lysosomal pathway by the lysosomal-METRIQ probe
Proposed pathophysiological mechanisms that could explain the presence or absence of response to treatment in myocarditis
Schematic drawing showing the role of MRP4 in regulation of Wnt/β-catenin signaling in the endometrium
A schematic model for the positive feedback loop between fibroblast activation and ECM deposition mediated by CD44-RhoA-YAP signaling pathway
TSP-1-CD36 signaling induces apoptosis of tumor-associated endothelial cells
Impact of ovarian cancer-exosomes on target cells during pre-metastatic niche formation
Differentially expressed genes involved in cell cycle pathway
EV production procedure.Exosomes, 50–150 nm, are initially formed by a process of inward budding in early endosomes to form multivesicular bodies
Control of fruit biochemical composition
Pathways for Nuclear factor Œ∫ B (NF-Œ∫B) signaling in the cytoplasm and the mitochondrion
The signaling pathway of CCR5 and neuronal plasticity
Sodium and potassium loci in behavior, thermoregulation, and weight loss networks
Metabolic map of the pathways responsible for surfactin biosynthesis
(a) Th17 cells produce a pro‐osteoclastogenic effect. SFB influenced the... (b) Tregs regulated the formation of osteoclast. Treg cell differentiati...
Basic schematic representation of the cAMP-PKA pathway (green) and three MAPK pathways in Candida albicans which are important for morphogenesis, adaptation to stress and survival
Red indicates significantly up-regulated transcripts
The p53 signaling pathway (hsa04115) is extended in the weighted network
The renin-angiotensin system and its bypass loops and converging signaling pathways can be targeted at different points
Graphical summary: the metabolic reprogramming during macrophage polarization induced by M-CSF (M2) and reinforced by IL-10 (M2c) leads to P2Y11 receptor upregulation
GRŒ±/PPARŒ± controlled points of interference with the TNF signaling pathway
The Epidermal growth factor receptor (EGFR) pathway in non-small cell lung cancer (NSCLC)
The EGFR pathway regulates PD-L1 expression in NSCLC
In EGFR mutant NSCLC without targetable resistant mutations, activation of YAP enhances the downstream genes expression of EGFs, ERBB3, ERBB4, CTGF, and CYR61 to form an autocrine loop and reinforce MAPK signaling pathway to induce cancer progression, drugs resistance, and immune escape
Transcriptional co-ordination between YAP1/Hippo and p53 family proteins in tumorigenesis or apoptosis
DNAM-1 signaling pathway leading to natural killer (NK) cell activation
The canonical Wnt/β-catenin signaling pathway
The crucial role of Wnt/β-catenin signaling pathway in multiple steps of bone sarcoma progression and metastatic dissemination
Proposed targeting approaches involving ACSL isoenzymes in cancer
Signaling pathway for GSSA via SCARB1 receptor from CD19+ lymphocyte
Scheme summarizing the protection of Aβ25‚Äì35-induced SH-SY5Y cell mitochondrial dysfunction by ginsenoside Re via inhibits ROS/ASK-1 dependent mitochondrial apoptosis pathway and activation of Nrf2-antioxidant response pathway
Schematic diagram depicting possible mechanisms involved in the anti-fibrotic effect of melatonin and PAA
Hypothetical pathway between autophagy and VEGF
ASD gene networks constructed with PASCAL associated genes and its FunCoup interactors
Tyrosine kinases in the development of atopic dermatitis
Diagram of the main molecular interactions implemented in the model
An illustration of the bidirectional interaction between Th17 and BEC
The signaling transduction cascades and cell-specific role of β-catenin-dependent canonical Wnt signaling pathway in regulating chondrocyte, synovial cells and osteoblast metabolism, whereby mediating the process of cartilage degradation, synovium inflammation, as well abnormally activited subchondral bone remodelling in OA development
Proposed model of the role of canonical and noncanonical wnt signaling pathway mediated network that regulating chondrocyte function, the activiation of Wnt signaling and their interaction between either canonical and noncanonical, or Hedgehog, MAPK, NF/Œ∫B, BMP/TGF-β/Smad and Notch signaling pathways, are assiciated with chondrocyte differentiation, hypertrophy, catabolism, anabolism and thereby involed in OA development, and marked with event-specific colored line or arrows
Interaction within TGF-b/BMP, canonical and non-canonical signaling pathway in osteoblast, in addition to induces DKK2 to inhibit the canonical Wnt signaling pathway, TGF-b/BMP signaling also up-regulates the expression of Wnt5a In osteoblasts, and subsequently stimulating the expression of a number of genes involved with osteogenesis
Regulating mechanisms of UCA1 in multiple human cancers
Proposed molecular mechanism of regulation of the pyrin inflammasome
EBV miRNAs Control Cell ApoptosisDeath receptors Fas, tumor necrosis factor-related apoptosis-inducing ligand receptors (TRAIL-R), and tumor necrosis factor receptors (TNF-R) form death-inducing signaling complex (DISC) upon interacting with their ligands, consequently inducing the caspase cascade
Dual sequential cell death checkpoints in the TNFR1 signaling pathway
Intrinsic intracellular signaling cascades of BDNF-TrkB and TrkB-A2a receptors
(A) Inflammatory pathway centered upon TNF in t... (B) The effects of dysbiosis on liver fibrosis... (C) Individual pathways of STAT-1-dependent NAS...
In vivo induction of demyelination by direct M
Schematic representation of mechanisms promoting macrophage phagocytosis of AC by lipid mediators
Mechanisms of IH protection against liver fibrosis
Circadian clock pathway mapped with relative expression levels (T1 vs
Transforming growth factor-β- (TGF-β-) induced EndoMT
KEGG pathway analysis for HepG2 cells depicting the upregulated genes in the TNF signaling pathway after the treatment with TIT3; the altered genes are marked
Biological processes associated with up-regulated genes after cecal ligation and puncture and back-regulated by landiolol infusion
The adenocarcinoma genotypes encode for transformation via the Ras pathway supported by the calcium pathway and the integrator complex
Several classes of drugs are tested in clinical trials aimed at either inhibiting catabolic signaling (drug name red) and thereby reducing protein degradation (orange), or stimulating anabolic pathways (drug name green) and thereby increasing protein synthesis (blue)
Summary of the classical Ras-Raf-MEK-ERK1/2signaling pathway
Summary of the functions of the ERK1/2signaling pathway
Summary of the role of the ERK1/2signaling pathway in CIRI
Modulation of the NFE2L2 pathway in fibroblasts
Inducers and regulators of IFN-Œ± production by plasmacytoid dendritic cell
Schematic picture of the type I interferon production and different nucleic acid sensors
Ingenuity Pathway Analysis (IPA) of the canonical pathways for the cetuximab-resistant cells based on (A) increased expression of uPAR and (B) the predicted signaling pathway for uPAR inhibition by resveratrol leading to suppression of cetuximab-resistance in cancer cells
Model of the cooperation between M and P proteins to inhibit different Jak-Stat-pathway steps
Proposed model of the combined effect of ROR1 inhibition and erlotinib treatment in non-small cell lung cancer cell lines via inhibition of the AKT/mTOR signaling pathway
Schematic diagram of the gene category of the NF-Œ∫B signaling pathway
The cartoon picture represents the mechanisms of inhibition of in-vitro metastatic potential after single and combined treatment
Major changes in network’s hub proteins (in red)
Genes found in the leading edge of the cell cycle pathway at 24h after FXR-L (panel A) and LXR-L (panel B) treatments are highlighted
Œ±vβ5 integrin/FAK-mediated phagocytic pathway in TM-1 cells
A putative model of positive and negative loops in the regulation of CREB-1 and CREB-2 expression and likely pathways by which Olibanum could control these loops
Insulin signaling regulates neuronal function
SDF-1 induces angiogenesis-related signaling pathways in HUVECs co-cultured with SMMC-7721 hepatocellular carcinoma cells (A)
A scheme based on our results: (A) Based on the recent findings, the MZ of the late larval lymph gland consists of two distinct domains
They promote the activation of insulin signaling molecules IRS1/AKT/GSK-3β
Enriched immunological pathway and genes
Interactions between VHL, HIF and the NF-Œ∫B signaling pathway
Identity checks in β-cell involving IRS-1 and KATP triggering pathway
Mechanism of response mediated by M1, M2, and M4 macrophages
Mechanisms of hepatocellular carcinoma development in the Mat1a knockout mouse
a Before binding by a Hedgehog family ligand (most often Shh, but also Ihh or Dhh), Ptch1 and presumably Ptch2 maintain Smo sequestered, by a currently unknown mechanism
Modulation of microglial inflammatory responses by IFN-β signaling
Illustration of a putative additional molecular mechanism for the ability of the inhibitory T cell signaling proteins CTLA-4 and PD-1 and the GPCR A2AR to diminish T cell activation leading to the enhancement of cancer development
Schematic KEGG map representations of signaling pathways involved in Alzheimer's disease (a), Parkinson's disease (b), and amyotrophic lateral sclerosis (c)
Overview of Ang/Tie2 signalling in the diabetic eye, including crosstalk with the VEGF pathway
Proposed model of dovitinib-mediated autophagy and apoptosis with regard to the SHP-1/p-STAT3 pathway in breast cells
Deoxynucleotide salvage and de novo synthesis pathways
Schematic representation of the main enzyme pathways involved in mitochondrial pyrimidine dNTPs metabolism
CNVs, SNVs/indels on histamine‚Äêrelated metabolism and signalling pathways
In cancer cells, the activated SMO and GLI could be suppressed by ITZ, these lead to the inhibition of target genes including Sox9/mTOR, cyclin D1, Wnt/β-catenin, Bcl-2/cyt C, PI3K/AKT/mTOR, vascular endothelial growth factor receptor 2 (VEGFR2), multidrug resistance protein 1 (ABCC1) to inhibit the growth and proliferation of many cancers in vivo and in vitro, arrest cell cycle, inhibit angiogenesis, and induce apoptosis and autophagy
Mechanisms of physiological and pathological hypertrophy
Molecular mechanism of miR-134 involvement in ESCC tumorigenesis
A schematic depicting the role of the C/EBP-β-lcn2 signaling pathway in MA-induced microglial apoptosis
Schematic representation of overlapping molecular mechanisms involved in the onset and progression of DM and AD that can be modulated by the specific action of phenolic compounds
Mitochondria and neurotrophic hypothesis in MDD pathophysiology
Subnetworks of special pathogenic pathways corresponded to different metastasis lesions
Linc00152 promotes the proliferation of HCC cells by activating the mTOR signaling pathway
Linc00152 promotes the proliferation of gastric cancer cells by regulating the PI3K/AKT signaling pathway
Hypothetic model of OME on colon cancer cells
Vascular inflammation during tumor cell extravasation and metastasis
Schematic representation of the TGF-ß/Smad signalling pathway and the possible targets of tamoxifen (TAM) and rBMP7 to prevent PF development
Schemes for nanoparticles loaded with specific agents to target TAM signaling pathways
Myofibroblasts were treated with curcumin
The signalling pathway induced by ManLAM
Red hexagons represent upregulated genes in mutant podocytes
The pathway was generated in IPA using data for concordant differentially expressed (Padj<0.05) genes across the two experiments.
Signal transduction pathways and transcriptional regulators affecting the filamentous growth of dimorphic pathopoiesis fungus in response to environmental conditions, which were reconstructed based on the predicted morphological shift in C
Schematic diagram showing the cardioprotective effects of YWPC on DOX‚Äêinduced cardiotoxicity
Model of the role and proposed mechanism of Wnt5a in psoriatic arthritis
The networks of DEGs involved in estrogen (a) and prostaglandin (b) signaling pathways
Overview of the Hedgehog signaling pathway
Most potent small molecules capable of inhibiting Hh pathway with their mode of action
The following model integrates published data and results of this study (highlighted with blue and red numbers respectively)
Anti‚Äê and proviral roles of autophagy in plants
Mucosal innate immune responses to STIs in the female genital tract that could potentiate HIV transmission risk
Schematic illustration of secretin receptor signaling in GnRH neurons
SUCO related genes involved in the cell cycle pathway
Colors indicate predicted effect of transcript on biological function or disease in center of circular diagram
Yellow box–target gene of one down-regulated miRNA; Orange box–target gene of two or more down-regulated miRNA
Schematic overview of glycolysis and mitochondrial respiration
Our proposed model of KRAS and TP53 oncogenes driving PDAC malignancy via the ARF6–AMAP1 pathway
Several metabolic mechanisms may provide an advantage to Tregs in the tumor microenvironment
Role of IL-1 cytokine family members in the immunological history of the hepatocarcinoma
Microglial signaling pathways determining development of cells with divergent abilities
RTT-related protein known functional interaction networks
Nobiletin-induced apoptotic pathway in bladder cancer cells
Local action of atrial natriuretic peptide (ANP) in cardiomyocytes
Schematic representation of inositol phosphatases in the plant inositol (Ins) signaling pathways under stress
piRNA and KRAB-ZFPs: two host systems that recognize and silence TEs
a–c, The modules are from the STRING protein–protein interaction networks and were generated using the consensus method
A solid line indicates interaction relationship between miRNA pairs, and a dash line shows the regulation relationship between a miRNA and its target genes involved in MAPK signaling pathway
A solid line indicates interaction between two miRNAs, and a dash line shows the regulation relationship between a miRNA in a Sub and its target genes belonging to Wnt signaling pathway
A schematic of the signalling pathways involved in AVE 0991-attenuated pyroptosis and hepatocyte damage induced by heat stress by inhibiting the ROS-NLRP3 inflammatory signalling pathway
Stress and depression drive an increase in corticotropin releasing factor (CRF) that activates mucosal mast cells and leads to an increase in gut permeability, coupled to gut dysbiosis and decreased butyrate production
Intracellular signaling involved in cardioprotective response stimulated by ischemic postconditioning (PostC) in cardiac cells
Upper, matrix metalloproteinase 1 (MMP1) cleavage of protease-activated receptors (PARs) result in increased Ca2+signaling
SUMOylation regulates gene expression during Acute Myeloid Leukemia (AML) response to chemo- and differentiation therapies
Role of SUMOylation in the regulation of Tax oncoprotein of the human T-cell lymphotropic virus type I (HTLV1) virus
The pro-angiogenic Ca2+ toolkit in vascular endothelial cells
Ca2+-dependent activation of the extracellular signal-regulated kinase (ERK) pathway and of the Nuclear Factor of Activated T-cells (NFAT)
The Ca2+ toolkit in endothelial colony forming cells (ECFC)
Protein functional interactome network for differentially expressed proteins identified in Pancreatic ductal adenocarcinoma (PDAC) tissue; down-regulated proteins (A) and up-regulated proteins (B)
Mechanisms of PTEN-mediated control of cancer stem cells (CSCs) hallmarks
BRAF-mediated signaling in normal and cancer cells
Expanding High Mobility Group A1 (HMGA1) chromatin functions
Model for the regulation of Keratin 6, 16 and 17 during skin wounding and in psoriasis
Figure depicts canonical hedgehog signaling pathway
Figure depicts pathways that cross-talk with Hh pathway leading to its non-canonical activation
Glucose metabolism is highly crucial for cancer cells
A simplified overview of the MAPK and PI3K pathway
Schematic illustration of the PI3K/Akt/mTOR signaling pathway
Direct and indirect epigenetic control of cellular metabolism
LRP6 and WNT/β-catenin pathway alterations in epithelial cancers
Role of heat shock protein 27 (HSP27) in different cellular apoptotic processes
Human oligodendrocyte precursor cells (hOPCs) incorporate and metabolize nervonic acid
After interacting with CD154, CD40 recruits and interacts with several adapter proteins, including TRAF1, 2, 3, 5 and 6
Pathways of androgen action in the Sertoli cell
The canonical WNT pathway in on and off states
Canonical WNT pathway components associated with disease
Drugs developed against canonical WNT pathway components
Schematic representation of signaling pathways downstream urokinase-type plasminogen activator (uPA) receptor (uPAR) and its co-receptors
Upstream regulators and signaling cascades linked to the hNgb protein interactors in a non-stress condition
Molecular interplay between estrogen, EGF, and Notch signaling pathways in FTEC ciliogenesis
Simplified scheme of the cellular metabolism pathways important for AML pathophysiology
Molecular mechanisms to increase glucose turnover in AML
Simplified model of fatty acid (FA) metabolism
Schematic of MAPK signalling in the context of wild type BRAF and mutant BRAFV600E
Adaptive response-mediated resistance to BRAF inhibitors in melanoma
miRNAs in regulating cancer stem cells characteristics: miRNAs can both inhibit or stimulate the development and characteristic of CSCs such as the ability of self-renewal, sphere formation, and chemoresistance through targeting signaling pathways involved in their survival and proliferation
Mechanistic overview of miRNA-mediated regulation of the stemness of cancer stem cells via targeting signaling pathways: miRNAs can act as both suppressive and enhancer of stem cells features such as self-renewal, sphere formation, cancer relapse, migration, invasion, and chemo- and radiotherapy resistance
DEGs’ products protein-protein interaction network for each mineral
BC subtype-specific EV protein kinase networks
miRNAs orchestrate T cell metabolic reprogramming
The circadian regulation of hepatic gluconeogenesis illustrates an example of bi-directional regulation between clock genes and metabolism
. Inhibition of anti-tumor immune response.
Metabolite pathway analysis with Pearson correlation coefficient only edges corresponding to correlations whose similarity was less than 0.5 are shown
Differentially expressed genes associated with the p53 signaling pathway
The representative miRNA-gene network interactions between the genes with an altered expression levels when comparing tumor to normal tissue and their respective miRNAs, generated using miRNet
Adenovirus-directed innate immunity through nuclear factor kappa-light-chain-enhancer of activated B cells (NFŒ∫B)
Hypothetical model for adenoviral regulation of stress-induced EGFR signaling through NFŒ∫B
Schematic of pathway inhibition by targeted agents and their effects on cell proliferation, apoptosis, metastasis and angiogenesis
Model of TNFR2-mediated regulation of NFŒ∫B transcriptions factors in Tregs
NMII knockdown cells show altered gene expression
Small molecules enhance knock-in efficiency
Schematic diagram depicting CCN1 induction of tip cell identity through interplay of integrin Œ±vβ3/VEGFR2 with Hippo pathway
Based on our findings, there are several crucial paths, including PI3/AKT/mTOR as well as HIF-1Œ± activation (in hypoxia) and inhibition (in normoxia)
Schematic diagram of the functional roles of SALL4 in cervical cancer cells
SnoRD126 activates the PI3K-AKT signaling pathway through FGFR2 and snoRD50A/B and affects the MAPK signaling cascades
Pre-synaptic and post-synaptic mechanisms regulated by PPT1
Schematic representation of altered metabolic pathways and associated circRNAs in cancer
circRNAs and the Warburg effect associated signaling pathways
AhR transcription in mammalian cells and the putative mechanism of AhR activation
Biosynthesis of AhR ligands from tryptophan metabolism
The role of WDR92 in the axonemal dynein assembly pathway
Intracellular signaling pathways of FFAR1-mediated HASM cell proliferation
Signaling pathways of proteins with different concentration
The schematic model of METTL3 in regulating CRC
Zn2+-induced mitochondrial dysfunction is a critical and targetable early contributor to ischemic neuronal injury
The cartoon schematizes some of the effects of mutant Kras in reprogramming amino acid metabolism
Proteins in the glycolysis, tricarboxylic acid, and oxidative phosphorylation pathways examined by the Ingenuity Pathway Analysis software
Schematic representation of pathway altered on both transcriptomic and epigenomic levels
Proposed model for the roles of Wnt/β-catenin signaling regulated by quercetin in protection of BBB breakdown
Schematic summary for the protective effects of escin on APAP-induced liver injury in mice
Intracellular signaling pathways involved in initiation and perpetuation of hepatic stellate cell activation
Schematic representation of the proposed mechanism of FAM289 in GBM cells
The alternative complement pathway in atypical hemolytic uremic syndrome and the associated genetic mutations.Note: Data from references 3, 16, 18-25.Abbreviations: CFB, complement factor B; CFD, complement factor D; CFI, complement factor I; CFH, complement factor H; MCP, membrane cofactor protein; THBD, thrombomodulin; MAC, membrane attack complex; CFHR, complement factor receptor; PLG, plasminogen; INF2, Inverted Formin 2; aHUS, atypical hemolytic uremic syndrome
In the DP-treated cells, DP preferentially recognized and activated EGFR receptors on the cell surface
Pattern Diagram of SFRP blocking the WNT pathway
Schematic representation of the potential molecular pathways representing potential targets for treatment in patients with ACC, based on the results presented in the current review
Bax/Bak proteins are activated by the action of BH3 only proteins Bid/Bim
The canonical pathway upon sensing DAMPs, PAMPs or other cytosolic disturbances results in the recruitment and activation of caspase-1 either directly or through recruitment of the receptor protein ASC
Predicted model for Ras-MAPK pathway controlling the differentiation of workers into neotenic reproductives
Epidermal growth factor receptor Pathway and its two pathways: Ras/Raf/Mitogen-activated protein kinases or PI3K/AKT
a | The subgranuŒØar zone (SGZ) of the dentate gyrus (DG) provides a unique microenvironment where adult neural stem and progenitor cells (NSPCs) undergo several consecutive developmental stages characterized by different cell types
Overview of predictive biomarkers for bevacizumab efficacy in breast cancer
Schematic representation of metabolism in WSSV-infected hemocytes showing the aerobic glycolysis, glutamine metabolism and lipogenesis pathways at the WSSV genome replication stage (12 hpi)
Schematic of SCD-associated oxidative stress pathways and antioxidant systems
Phosphorylation of central carbon metabolic enzymes
P2X7 activation induces cell death via different molecular pathways depending on the cell type
Role of Fyn in misfolded Œ±-synuclein (Œ±Syn)-mediated NLRP3 inflammasome activation
Modular network regulation map of gene-related ncRNA/TFs
HMGB1, as a priming signalling, involved in the stress-neuroinflammation-mesolimbic dopaminergic pathway
Activated Nrf2 entered the cell nucleus after dissociating from Keap1 suppressing protein, and combined with Maf protein in the nucleus to form a heterodimer and then combined with ARE DNA sequence, therefore, initiated gene transcription controlled by AREThis path is called as Keap-Nrf2-ARE pathway
Identification of DEGs relevant to protein processing in the endoplasmic reticulum pathway
Pathway map assigned for MAPKs signalling
Seminal fluid and semen induce expression changes in honeybee queen brains for genes mapping to the phototransduction pathway of Drosophila in both Experiment 1 (A) and Experiment 2 (B)
Schematic representation of the signaling cascade activated by the CaSR that induces the arrival of ZO-2 to TJs
Metabolic pathway of aerial and submerged mycelia in the liquid surface culture of Cordyceps militaris
Mechanism of ROCK1 promoting tumor cell migration, invasion and progression in NSCLC
The canonical mechanism of TH action involves uptake of L-thyroxine (T4) or triiodothyronine (T3) into the cell by TH transporters, including the monocarboxylate transporter 8 (MCT8), L-type amino acid transporters (LAT) 1 and 2, and organic anion transporter protein (OATP) 1c1
Complement-platelet interactions that can facilitate an inflammatory response that favors atheroma formation
The exposure to high fat diets over time, enriched in saturated fatty acids, would promote the glial activation and an increased mitochondrial oxidative stress
Molecular mechanisms of KLF15 in renal fibrosis and mesangial pathology
Proposed model illustrating the roles of CHL1 during NPC carcinogenesis
Model for how the RAM (regulation of Ace2 and morphogenesis) and the CWI (cell wall integrity) pathways regulate the transition between growth and quiescence
Simplified schematic of the RAS-RAF-MEK-ERK signaling pathway, the mutation sites and frequencies of key effectors, and their representative targeted inhibitors
A general, schematic diagram of the modeled process is shown below the Petri net
Small circular nodes indicate ‘and’ rules whereas multiple incoming edges to a rectangular node indicate ‘or’ rule
TAAR1 signaling pathway/apoptotic pathway components
DNA single-strand break and double-strand break repair pathways
The cross-talk between DNA damage and immune response
The summary of mammalian Sia metabolism and the Neu5Ac-activated signaling pathway in cardiomyocyte
Results of network analysis: differentially regulated proteins from the SILAC approach are indicated in green (TCam-2) or in red (NTERA-2)
Schematic representation of CD28 KO reverses lung blast injury by the PI3K/Akt/FoxO1 signaling pathway
Tumor Necrosis Factor Receptor 1 (TNFR-1) Signalling Pathway
Hotnet2 pathway analysis including resistant CNV and resistant mutations (P < .01)
A major hallmark of immunosuppression in the TME through diverse pathways in EGFR-mutant NSCLC
Intrinsic cancer cell pathways mediate the regulation of PD-L1 expression and MHC in EGFR-mutant NSCLC
A schematic diagram of EB virus involved in the G1/S transition
Elevated FAM83A expression in pancreatic cancers is driven by a MEK/ERK-JUNB-driven feed-forward signalling loop
Endoplasmic reticulum (ER) stress-mediated inflammation
Signaling pathway of DNA damage response (DDR) in the context of chromatin
Signaling pathways involved in the switch between proliferation and dormancy
Schematic representation of signaling pathways involved in the AVP-dependent myogenic differentiation
Schematic representation of the Fas/Fas-L pathway
The different expression of HH (hedgehog) signaling
Canonical and non-canonical signaling of FGF23
Syntenin-mediated signaling in the regulation of membrane structure and cell motility
Schematic summary of the molecular pathways of F
A model for how insulin-stimulated cleavage of TUG and subsequent trafficking of GSVs coordinately regulates multiple physiologic effects
A proposed signaling pathway involved in EXD against TNF-Œ±-induced cell damage
Erythropoietin (Epo) binds to the Epo receptor (EpoR) to activate erythroid-specific gene transcription (EpoR, globins, glycophorin A (GPA), and miR-144/451) by GATA-1, resulting in hemoglobin (Hb) production
KEGG Pathview readouts of DEX vs Control-associated differential gene expression
Translational regulation in response to glucose availability: The presence of glucose results in the activation of PKA promoting high levels of protein biogenesis
Active constituent-protein targets-signaling pathway network of frankincense–myrrh compound against breast cancer
Primary tumours secrete various growth factors, cytokines and enzymes (vascular endothelial growth factor A (VEGFA), placental growth factor (P1GF), transforming growth factor-β (TGFP), tumour necrosis factor (TNF) and lysyl oxidase) and shed extracellular vesicles into the circulation that systemically impact the lung microenvironment
LiCl modulated macrophage polarization to promote the osteogenic differentiation of rBMSCs via the suppression of ERK and p38 phosphorylation.Notes: LiCl exerted an immunomodulatory effect on macrophage polarization and attenuated Ti particle-induced inflammatory responses in vitro and in vivo, and generated an immune microenvironment to improve the osteogenic differentiation capability of rBMSCs
Possible integrated mechanism of cell injury and its relationship with microcephaly ZIKV-induced and cell death
A schematic description of TLR7-mediated enhancement of CD8+ T cell function
A brief conclusion of miR-27a in regulating cell signal pathways Panel gray, miR-27a can regulate Ras/MAPK/ERK pathway to active key gene such as c-myc
Interaction between BAs and the TGR5 signaling pathwayThese are three major metabolic pathways in the TGR5 signaling pathway
Summary of molecular basis on which epigallocatechin-3-gallate (EGCG) prevents chronic kidney disease (CKD) and renal fibrosis based on preclinical evidence
This is a simplified model of the potential interactions of TGFβ, AHR, and Wnt signaling pathways in TED, and how the PPIs may be signaling through AHR affecting Wnt signaling and preventing TGFβ-myofibroblast formation
Tbx1-Isl1-Met genetic pathway regulates only a subset of CPM-derived muscles
A schematic diagram of the pathogen-derived molecules used to escape cytokine-sensing pathways in cells
(A) MiR-155 is expressed in plasma (P), monocytes, fibroblast-like synov... (B) MiR-146a was expressed in PMBCs, monocytes, synovial fibroblasts, an...
Peptide/amino acid transport and metabolism and cofactor synthesis in Gs and Au cells
Engineering the mitochondrial isobutanol biosynthetic pathway in a xylose-utilizing strain of S
Common signaling pathway for IL-1 family cytokines
A mechanism diagram depicting that the miR-193a-5p/DPEP1 axis affects the progression of HB through the PI3K/Akt/mTOR signaling
Annexin A1 binds to membrane FRP2, a G-protein coupled receptor, and activates G protein
STRING connectivity network demonstrating a protein–protein interaction network of predicted functional partners for differentially expressed genes in the brown module
Effects of Ginsenoside Rb1 prevent the steroid-induced avascular necrosis of the femoral head through BMP-2 and VEGF signaling pathway
Signaling pathway regulation network of the three validated differentially expressed tRFs
Main synthesis pathway of n-3 long-chain PUFA-derived lipid mediators
Hypothetical mechanism underlying the inhibition of palmitic acid-induced lipid accumulation by apigenin in HepG2 cells
Adipocytes represent a central player in the creation of the metabolic tumor microenvironment in the omentum during ovarian cancer metastasis
Schematic overview of genetic and epigenetic abnormalities in Wnt pathway components in MM and drugs that target canonical Wnt signaling
PPI network of DEGs.Notes: Circles represent genes, lines represent the interaction of proteins between genes, and the results within the circle represent the structure of proteins.Abbreviations: PPI, protein–protein interaction; DEGs, differentially expressed genes
The 20 top hub genes in PPI network.Notes: The diamond icon represents the downregulated hub genes, the circle icon represents the upregulated hub genes, the size of the icon represents the strength of nodes that interact with other genes, lines represent the interaction of proteins between genes.Abbreviation: PPI, protein–protein interaction
Illustration of pathway signalling where phosphorylation signalling PTMs have been sequenced and annotated in melanoma tumours from patients
The mitogen-activated protein kinase signaling pathway in lung squamous cell carcinoma
Glutamine-dependent regulation of BMSC osteogenic and adipocyte differentiation
KEGG pathway analysis of the differentially expressed genes in head and neck squamous cell carcinoma
Important signaling pathways that govern the differentiation of pancreatic conversion and the mechanism of action of different small molecules and peptides reported on pancreatic differentiation from MSC
The signaling pathway proposed in this study
Abbreviated summary of monocyte activation pathways
Schematic representation of exemplary metabolic pathways transcriptionally affected by oleuropein in Lactobacillus plantarum WCFS1
Functional overview of the embryonic complement system
Schematic overview of gene expression regulation of fatty acid oxidation and tricarboxylic acid (TCA) cycle in tPVAT and IAT
Mechanistic network analysis predicts multiple affected signaling networks
Enrichment in multiple cancer-associated networks in breast cancer
Different ncRNAs regulate PDCD4 in mutiple ways
Scheme for the MKK7-dependent JNK pathway
Putative scheme for the MKK7/JNK signaling pathway
CBS deficiency suppressed erythropoiesis mainly by disrupting expression of heme biosynthetic enzymes and transporter
(A) Shared inactivating mutations indicate that AANAT (aralkylamine N-ac... (B) Pathway to synthesize melatonin from serotonin and the main sites of...
A suggestive model for receptor-mediated pathway involved in CD biology
Strategies for immunomodulation to mitigate periprosthetic osteolysis induced by wear particles
Putative mechanism of necroptosis and relative inflammatory responses during the development of CCI
The whole driver PC3-represented PCa signaling pathway
Cyclooxygenases (COX) convert polyunsaturated fatty acids (PUFAs) to prostanoids
Two representations of proteins involved in GBM
Overview of the MAPK/MKP3 signaling network and application of caged cysteine toward caging the catalytic site of the phosphatase
DEGs are potentially related to Alzheimer’s relevant pathways and functions
Mechanism of neuroprotective effects of genistein against neuropathological insults of Alzheimer’s disease
Mechanism of neuroprotective and antioxidant effects of genistein by interacting with estrogen receptor
Regulation of the main phases of the autophagic pathway by the C2‐WW‐HECT E3s
SMI suppressed Ang II–induced cardiomyocyte hypertrophy and apoptosis through the activation of the AMPK signaling pathway via energy-dependent mechanisms
Overview of key metabolic pathways in neutrophils
Significant metabolic pathways, Ubiquitin‐mediated proteolysis pathway and Adherens junction and Wnt signaling pathway for regulated genes associated with IS‐SM when compared to IS‐NSM
Relationships of the top differentially expressed genes within the top GSEA gene sets
Concomitant administration of GNF-2 and cyclophosphamide results in the inhibition of the AKT-FOXO3a signaling axis and DDR, thereby preventing cyclophosphamide-induced apoptosis of oocyte reserve
. A network analysis of predicted targets of miR-29-3p, miR-584-5p, and miR-1247-5p as performed by ingenuity pathway analysis (IPA).
Possible mechanisms contributing to the inhibition of fat synthesis and glucose utilization of M
Major biological processes highlighted by pathway analysis of genome-wide association studies including 29 391 coronary artery disease cases and 66 819 controls
Cell cycle‚Äênon specific mechanisms for the resistance to CDK4/6 inhibitors
The effect of corilagin on the Notch-mTOR signaling pathway in cholangiocarcinoma
The effect of corilagin on the TGF-β signaling pathway in ovarian cancer
The RAS/RAF/MEK/ERK pathway: Upon growth factor (GF) activation RTKs auto‐phosphorylate and recruit the SH2 domain‐containing GRB2, which interacts with the guanine nucleotide exchange factor SOS that induces release of GDP from RAS, which subsequently binds GTP
The cyclooxygenase (COX) pathway and prostaglandin E2 (PGE2) signaling
Canonical and noncanonical signaling pathways of NOD1 and NOD2
Role of TRPML1 in the regulation of ERK signaling in cells harboring HRASG12V mutations
The role of omental adipocytes in tumour development and metastasis.In omental adipocytes exposed to asbestos, MCP-1 secretion is increased and adiponectin secretion is reduced, resulting in an inflammatory reaction and mesothelial cell hyperplasia that induces the development of mesothelioma
a miR-708 expression gradient is reduced during the transformation from normal prostate epithelial cells through adenocarcinoma cells to NEPC
Meanwhile, it supposed a transcript regulation function of ETS1 in TGM2, indicating the indirect inhibition effect of miR-532-3p on TGM2
Manipulation of the interferon signaling pathway in myeloid cells
BK protein (preferentially via C-terminus of BKŒ±) binds integrin β1 in osteoblasts
Tumor microenvironment shapes NK cell metabolism and effector functions
Anti-autophagic and anti-apoptotic pathway activated in human DCs by P
. The mechanism of BRAFV600E mutation negatively regulates sodium iodide symporter (NIS) and Integrin targeted imaging.
The possible mechanism of action underlying the protective effects of maltol against APAP-induced hepatic injury through inhibition of oxidative stress-mediated activation of the NF-Œ∫B pathway and apoptosis and regulation of the PI3K/Akt pathway
Proteasome pathway mapping of altered genes in DLD-1-miR-21 cells
Genetic network and functions of PSGs (positively selected genes) related with the KEGG pathway of the PPAR signaling pathway, fat digestion and absorption, vitamin digestion and absorption
Anti-apoptotic and cell survival activities of some HSPs in cancer
HSP90 functions as a mediator of many oncogenic and signaling pathways []
Flavonoids as anti-diabetic agents: Modes of Action
Pathway of the investigated genes involved in apoptosis
Schematic summarizing the molecular mechanisms contributing to cancer progression
Receptors used by chemerin, visfatin, resistin and apelin for their signaling pathways
Apoptotic pathways triggered by inosine 5‚Ä≤-monophosphate dehydrogenase (IMPDH) inhibitors
The metabolic pathway of classic and non-classic androgens
A simple depiction of signaling pathways for the activation of classical NLRP3 inflammasome (canonical and non-canonical) and alternative inflammasome
Transforming growth factor β (TGFβ) family SMAD-dependent signaling
Transforming growth factor β (TGFβ) family SMAD-independent signaling
Effects of the different Transforming Growth Factor β (TGFβ) family members on articular cartilage biology and osteoarthritis (OA) development
Interference of hepatitis C virus (HCV) with the nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2)/ Keap1-signaling pathway
miRNA-responsive biological pathways and the presence or absence of interactions between its genes and the transfected miRNA
The pathway shows the influence of adipocytes on cancer
Effects of anthocyanins on pro-survival and pro-apoptotic signaling pathways
Differentially expressed genes in the neurotrophin signaling pathway between mandarin fish at CG and LG from a transcriptome analysis
Differentially expressed genes in the cyclic AMP (cAMP) signaling pathway between mandarin fish in the control group (CG) and the learning group (LG) from a transcriptome analysis
The substance P/neurokinin-1 receptor (SP/NK-1R) system regulates several cell signaling pathways involved in cancer progression
Our model of the BRAF mutation positive mitogen-activated protein kinase (MAPK) pathway signaling mechanisms
Hepatic synthesis of glutathione and nutritional substrates, co-factors, and other nutrients that influence metabolism
The specific crosstalk network of each breast cancer subtype
The mechanism of optimal therapeutic drugs in each subtype of breast cancer
Basics of transforming growth factor β (TGFβ) signaling
TGFβ signaling in cholangiocarcinoma (CCA) progression
Three major branches of the Unfolded Protein Response (UPR) signaling pathway and their interconnections
Biological origin of free radicals and their effect on cell viability
Bone metastasis physiopathology: implication of cancer cell-microenvironment interactions and therapeutic targets
Regulation of EMT at different molecular levels: upregulation of the WNT pathway, PI3K/AKT pathway, and RAS/RAF/MEK/ERK/MAPK pathway and downregulation of the TGF-β/Smad pathway lead to the activation of EMT through downregulation of E-cadherin
The DNA damage response network in SCLC cells
The infectious spleen and kidney necrosis virus (ISKNV) induced the changes of glucose metabolism in the cellular transcriptomic, proteomic, and metabolomics of Chinese perch brain cell line (CPB) cells at its replication cycle
Key metabolic remodeling and potential therapeutic targets in glioblastoma (GBM)
Apoptosis pathways (hsa04210) and targets of cordycepin
Hyperglycemia associated metabolic reprogramming in cancer cells and potential targets
Molecular mechanisms involved in inflammasome activation
Schematic representation of chemotherapy-induced apoptosis and pyroptosis in cancer cell
The key metabolic pathway and regulatory network in mutant ptsd1
Proposed mechanism of coelonin inhibiting LPS-stimulated activation of NF-Œ∫B and inducing G1 phase cell-cycle arrest in RAW264.7 cells
Scheme of the de novo synthesis pathway of glutathione
Diallyl trisulfide (DATS) protected the brain tissue against the damage induced by ischemia/reperfusion (IR)
Schematic drawing presents the detailed signaling pathways of breast carcinogenesis
Schematic diagram for apoptosis induced by KRG extract
Proposed action mechanism of 6SL in TP-induced BPH rats and BPH-1 cells
A map of potential pathways and their potential interactions activated by a soluble factor- radiation-induced bystander effect (RIBE) signal
A simplified TGFβ pathway leading to p21 expression
A hypothetical signalling pathway that illustrates how the various pathways in this review may be connected, which is partially informed by preliminary research
The proposed cell signaling pathways used by TC7 to induce PCa cell apoptosis, cell cycle arrest, and metastasis inhibition through the regulation of p38/cyclin b1/CDC2, and p53-dependent GADD45A/PLK1, p38/P53/caspase 8, and p38/VEGF-1/MMP-9 signaling pathway
The TLR4–p38β MAPK–C/EBPβ signaling pathway mediates the coordinate activation of UPP and ALP in cancer-induced muscle catabolism
Pathway of energy metabolism and ginsenoside synthesis
Molecules and cellular pathways that contribute to thyroid cancer development
Co-expression analysis of the DEGs in Złotnicka White pigs
Co-expression analysis of genes overexpressed in Pu≈Çawska pigs, characterized by high feed conversion values
The string network of proteins (encoded by the differentially expressed genes (DEGs)) involved in signalling pathways
Rational combinations of PARPi with other targeted agents
Scheme of the in silico analysis leading to SNP identification and KASPar™ analysis
AKT2 and MAPK pathways were spontaneously overactivated in CDDP-R/Rad-R BE(2)-C cells and CDDP-R/Rad-R SK-N-AS cells growing up in neurosphere media
The complement system and crosstalk with other innate immune effector systems in liver IRI, regeneration, and transplantation
IGF signalling pathway alterations occurring in cisplatin‚Äêresistant TGCT
KEGG pathways for TCA cycle and retinol metabolism in the T 6 vs
The mutual interactions of the mitochondrial compartment with hepatitis viruses and the consequences on the infections
Clinal candidates in the insulin/TOR signaling pathway
Canonical Wnt/β‐catenin and divergent signaling pathways
Overview of the main strategies of immunomodulation
Overview of the core cell metabolic pathways
LRRK2 substrates involved in vesicle trafficking and synaptic transmission
A schematic diagram of Pyroptosis pathways
Network visualization analysis of “potential lipid markers-lipoproteins-TLR4/MyD88 signaling pathways” for anti-inflammatory effects of HLJDD
Mechanisms of immune exclusion through the Wnt/beta-catenin pathway
Effect of WNT signaling on cancer immunosurveillance
A proposed signaling network of regulating the formation and development of seminal vesicle tumors in TRAMP mice
The proposed regulatory mechanism of melanin-regulating signaling pathways in C
The proposed mechanism through which Fucoidan-Sargassum impedes invadopodia formation in HCCLM3 cells
The role of cyclin D-CDK4/6-INK4-Rb pathway in breast cancer
Signaling pathways associated with tumorigenesis and combined treatments that alleviate drug resistance
Kyoto Encyclopedia of Genes and Genomes pathway analysis in SK-BR-3 vs
Mechanism of neuroprotection mediated by dexmedetomidine in astrocytes and MCAO rats
Proposed working model of œâ-3 PUFAs induced inhibitory effect on inflammation and autoimmunity
The activation of serotonin receptors (5-HT-R) initiates a signaling cascade that leads to the activation of extracellular signal-regulated kinases (ERK)
Metabolic pathway scheme summarizing changes in carbon, energy and photosynthesis metabolic pathways during tomato fruit ripening
Schematic view of the role of Œ±vβ3-int in PD-L1 expression and antitumor immunity
PPI network generated for the proteins encoded by the eight statistical driver genes
Innate immune pathways inhibition by calicivirus infection
Schematic representation of the core components of the Hippo signaling pathway
Transcriptional profiling of enzymes involved in type II fatty acid synthesis (FASII), glycerolipid synthesis in plastid (GLSp) and cytosol glycolysis (GLSc), and beta-oxidation
Overview of human adenovirus induced cell signaling and downstream immune responses in human keratocytes, highlighting the centrality of Src kinase
The impacts of mutations in the TGFβ signaling transduction components contribute to PDAC development
Schematic diagram of enriched extracellular matrix organization pathway in non-type subtype of bladder carcinoma cell lines
A schematic model of the mechanisms of the ANA-induced apoptosis and its synergies with the cell death inducing cytokines
Intracellular peptidoglycan (PGN) is detected by intracellular receptors and activates the NF-Œ∫B signaling pathway in Drosophila melanogaster and human enterocytes
A generalized Toll-like receptor signaling mechanism, adapted from []
Scheme illustration demonstrated that nHA-coated BCP scaffolds could stimulate osteogenic differentiation via BMP/Smad signaling pathway in vitro, and induce ectopic bone formation in vivo
PPI networks and GO and KEGG pathway analyses for the top two positively co-expressed hub modules of SNHG7 in thyroid cancer
Bioinformatics analyses for the top two negatively co-expressed hub modules of SNHG7 in thyroid cancer
Pathway analysis shows the identified proteins and their respective interactions
Schematic illustration of VEGFR structures and their specific ligands
Shh signaling pathway in hepatocellular carcinoma
Schematic overview of the TLR4 signaling pathway
AKR1C1-3 are involved in a pathway with 44 unique interactors
Complement activation triggers neuronal damage
(a) The illustration of human IgG1 structure with N-glycan attached at A... (b) The schematic diagram of antibody-dependent cellular cytotoxicity (A...
Schema of ACh-muscarinic acetylcholine receptor 3 (M3R) signaling pathway in gastrointestinal (GI) tumor cells
Physiological reconstructions based on RAST annotations and Pathway Tools metabolic modelling
Nephrin Interactions is an example of a top-ranked light pathway, defined as a pathway highly covered with HNSCC mutations (~100pct) and frequently mutated in the patient cohort (36pct)
The calcium signaling pathway is overrepresented in the specific differentially expressed genes altered by alfalfa intervention during the preweaning period
A model illustrating BEFV-induced autophagy signaling pathways
Schematic model of the effects of ASA in SK‐N‐SH (N) cells
Schematic outline of major Btk signalling cascades
Involvement and regulation of lncRNAs in M1‚Äêlike macrophage polarization
AT-rich interactive domain 1A (ARID1A) chromatin remodeling abnormalities in ovarian clear cell carcinoma (OCCC)
Signaling pathways participating in the function of cadherins in cancer
Cell type-specific signaling pathways activated by GPER on neurons and astrocytes.On neuronal cells the activation of GPER is associated to an increase of neuronal survival, via the increase of cAMP levels and the activation of MAPK and CREB pathways, and via the activation of PI3K pathway
The neuro-glial coagulonome (NG-coagulonome) in the peripheral nervous system (PNS) and central nervous system (CNS)
Proposed model for the role of RarŒ± in adrenocortical development
The schematic of chemical-driven cell fate change and expansion
Citrate produced through mitochondrial metabolism can enter the fatty acid synthesis pathway
The theoretical regulation of bevacizumab on claudin5 signaling pathway
Diagram of Ras/Raf/MAPK and PI3K/AKT/mTOR signaling pathways
The protein–protein interaction (PPI) network of the set of DEGs/DEPs identified in the overrepresented GO Immune System Process terms
Mechanisms of action of methylxanthine (MTXs) in glioblastoma (GBM)
The mitogen-activated protein kinase (MAPK) signaling pathway and related miRNAs
Ciona robusta cardiopharyngeal gene regulatory network and tunicate phylogeny
Biological applications of light‚Äêinduced dimerization systems
Oncogenic activity of Bacteroides fragilis and Salmonella enterica
Schematic model of the evolution of CIN+ tumors
The related cytokine signaling pathways and transcription factors involved in Th9 cell differentiation
Adverse outcome pathways (AOPs) for select chemical pathways of thyroid disruption, including (A) rat thyroid follicular cell tumors linked to chemical inhibition of TPO; (B) impaired cognitive functioning in mammals linked to chemical inhibition of TPO; and (C) hearing deficits in mammals linked to inductions of TH catabolic pathways
TNFα and cAMP-PKA signal pathways exert opposite effects to regulate GD3 synthase gene expression in human melanocytes
Targeting NRF2 antioxidant pathway for IDH1-mutated cancers
The colorectal cancer pathway enriched in KEGG
Scheme of differentiation of M cells in PP
Schematic representation of parallel pathway in detoxifying environmental electrophiles
Wnt signaling with two intersecting networks: Canonical Wnt (or β-catenin-dependent) and non-canonical Wnt (or β-catenin-independent) pathways
Protein-Protein interaction network and 5 identified sub-networks of TTR-mRNAs
Five functional lncRNA-mRNA trans regulatory network
Scheme of the parietal cell of a gastric gland
Schematic representation of the signaling pathways regulating TREM2 phagocytosis and TREM2 modulation of NFŒ∫B phosphorylation/activation
Diagram illustrates the mechanisms of insulin resistance
Protein-protein network analysis using the DE genes (log2 fold > 2 and < 2) in the transcriptomic profiles of the cows with PTB-associated lesions versus the control group
Conceptualized overview of the association between inflammation and angiogenesis
Flow chart of the DARPP-32-CaN pathway in the Cys311 variant of DRD2
Key metabolic gene sets are differentially regulated in subcutaneous adipose tissue after 36‚ÄØh fasting vs control study (horizontally) and in LBW vs NBW men (vertically)
Core molecular mechanism of non-apoptotic regulated cell death
Red proteins are upregulated in cancer patients, green proteins are downregulated in cancer patients
Platelet‐derived growth factors from breast cancer or neuroblastoma stimulate the platelet‐derived growth factor (PDGF) receptors and initiate immune and tumorigenesis response
KEGG pathway map for MAPK signaling for flowering Chinese cabbage libraries
Receptor composition of IL-12 family members and related cytokines
Proposed bi-phasic model for the role of Egr-1 in activation of DCs and down-modulation of DC maturation upon challenge with T
The RAS pathway shapes interactions between cancer cells and the immune microenvironment
Basics of nicotinamide adenine dinucleotide (NAD+) metabolism in plant cells
Schematic presentation of Nipah virus (NiV)-induced modulation of type I interferon (IFN-I) production and signaling
TSHR mediated signaling induced OF proliferation through Akt signaling and induction of miR-146a and miR-155
COPD creates a favourable microenvironment for lung cancer initiation and progression
Schematic representation of signalling induced by adhesion molecules inside the host cell
Additional gut microbial metabolites regulate host immunity and metabolism
The cAMP signaling pathway and its relationships with β2-AR, GPCR, and potassium channels
The Fas-FasL pathway and its roles in cell death and cell survival
The Ca2+signaling pathway and the roles of CD38, Ca2+ channels, and G-protein-coupled receptors
Signaling pathways contributing to mucus production
The potential mechanisms of fluoxetine in the remission of AD
MDV DNA or tumor-derived DNA is recognized by cytosolic DNA sensor cGAS, which produces cGAMP for STING activation and IFN-β production
TGF-β receptors activate Smad signaling and non-Smad signal transduction pathways
Schematic representation of the pathway leading to IL-1β release from NK92 and its inhibition by DMF or MMF
Molecular mechanisms involved in the proliferative and cytokine response of hypoxic BMSCs
An overview of myocardial energy substrate utilization
Pathway signaling network generated from the genes located within the top 100 most differentially methylated CpG islands
Schematic representation of the most significant Ingenuity Pathway Analysis (IPA) network of differentially regulated proteins in the MHO group compared to those from the MUHO group
Schematic illustration of AMPK signaling pathway following EPA treatment in skeletal muscle cells
Summary of data showing TGF-β1 recruitment of miR-143 and miR-145 to RISC to destabilize CFTR mRNA and impair the corrector/potentiator-mediated rescue of F508del-CFTR
Endogenously derived chemerin mediates a tumor-suppressive effect through inhibition of Wnt/β-catenin signaling in adrenocortical carcinoma
MiR-1 targets the calcineurin–NFAT signaling pathway; miR-1 plays a protective role in cardiac hypertrophy by decreasing the expression of NFAT
The anti-hypertrophic role of miR-133a is mediated by inhibition of Gq-protein and PKC pathways
The model structure consists of HIF-1Œ± signaling, tumor signaling, and ATP depletion modules
External aggressors increase ROS production in the skin, which induces downstream MAPK signaling pathways, leading to an activation of NF-Œ∫B and AP-1
A schematic diagram of the JNK signaling pathway promoting cell death in ovarian cancer
JNK signaling pathway mediated drug resistance
Probable mechanisms through which royal jelly (RJ) and its components extend lifespan
Mechanistic network analysis predicted by Ingenuity Pathway Analysis
Central carbon metabolism and catabolite control protein CcpA
Metabolic pathway of linoleic and arachidonic acid
Ras signaling pathway shown as an interacting network
PVT1 participates in the downstream signaling pathway of c-Myc by regulating key molecules
Immunometabolic changes associated with DC maturation
Proposed biosynthetic pathway for compounds 1–8
Schematic diagram showing the molecular mechanism of BB decreases lipid accumulation and inhibits obesity by down-regulating multiple transcription factors, inhibiting the synthesis of lipid accumulation proteins, and promoting the expression of lipid-degrading proteins in 3T3-L1 cells
Biosynthesis of glucoraphanin, its hydrolysis to form the isothiocyanate sulforaphane, and metabolism of sulforaphane
Mechanism of regulatory actions of E2 on MAP1A and hemoglobin Œ± transcription
Schematic presentation of the signaling pathways involved in erinacine A‚Äìinduced cell apoptosis in human DLD-1 cancer cells, and the effect of erinacine A on the activation of the JNK/p300/p50 NFŒ∫B pathways, which leads to TNFR, Fas, and FasL expression with the implications of histone H3K9K14ac (Acetyl Lys9/Lys14) in human DLD-1
Major G protein-coupled receptor (GPCR) signaling pathways
Model of Anti-tumor Effects of Reovirus Combined with KU60019In general, the phosphorylation of ATM protein is induced when DNA double-strand breaks are caused by UV or radiation
The 2D cell culture environment and 3D cell culture environment reacted to rapamycin and BCG treatment, and there were strong differences
The molecular mechanism of miR-129-5p regulation of ZIC2 expression and the Wnt/β-catenin signaling pathway in PCa
Notch pathway amplifies intrinsic noise by interactions that improve the efficiency of global protein synthesis
Notch-induced autophagy and translational noise as destabilizers of cellular memory
Noise-induced bistability and resolution of fate dichotomies
The network structure of the 66 genes (left figure) and the top 12 selected genes listed in  (right figure) from KEGG “Drug metabolism-cytochrome P450” pathway, extracted using the R package KEGGgraph
Canonical Wnt signaling manipulation during bacterial infection of epithelial cells
Canonical Wnt signaling manipulation during Rickettsia spp
Canonical and non-canonical Wnt signaling manipulation during E
Canonical and non-canonical Wnt signaling manipulation by pathogens occupying an extracellular niche
GCs affect cross-talk of bone cells and their communication with muscle, vasculature and myeloid cell-derived osteoclasts
Schematic representation of important metabolism-related cellular signaling cascades where FKBP51 was shown to play a decisive role (see main text for further details)
The figure shows transcripts significantly downregulated (green symbols) or upregulated (red) in the Toll-like Receptor Signaling pathway, as described by Ingenuity Pathways Analysis software
Schematic model of plant innate immune defense process against Sclerotinia sclerotiorum infection
Proposed role of the immunogenic cell death in pemphigus foliaceus
Hypothetical model of action of EC-7072 targeting the BCR signaling pathway in CLL cells
Engineered cardiac tissues (ECTs) generated in Biowire II platform have canonical responses to compounds that affect contractility via physiologically relevant pathways
Non-genomic mechanisms of thyroid hormones action in the brain
The proposed signaling pathway of the study
KEGG pathway enrichment analysis of methylated regions–
The miRNA–mRNA interaction networks containing five cell proliferation and differentiation related pathways
The miRNA–mRNA interaction networks containing two matrix connectivity (a) and (b) represent the miRNA–mRNA interaction networks with three cell junction (focal adhesion, ECM-receptor interaction, gap junction) and two matrix connectivity (tight junction, and adherens junction) related pathways, respectively
Schematic representation of the principal signaling events occurring during fluid shear stress in bone cells
GSK3 regulates cell death, renewal, and differentiation
The probable mechanisms of the effects produced by lncRNAs on SCI
The schematic mechanism of matrine signaling pathway that inhibits cell growth and leads to cell death in HL-7702 cells
The Pathview analysis of the NF-Œ∫B signaling pathway
Schematic illustration the role of ES-EVs on MSCs
Mechanisms of AA-induced vasorelaxation and relationship to aldehyde metabolism
Orexins/OXR system-modulated signaling patways involved in anti-inflammatory, neuroprotective and anti-tumoral effects
Functional consequences of VPAC receptors signaling
VEGF (vascular endothelial growth factor)‚Äêangiogenesis signaling and cell cycle regulation pathways
Schematic diagram of the proposed mechanisms for the anti-neuroinflammatory effects of CBL
Cell signaling regulation of endogenous H2S in the central nervous system
A schematic model of JMJD2C promoted CRC metastasis by regulating the histone methylation level of the MALAT1 promoter and enhancing β-catenin signaling pathway
Macrophage infection affects host metabolic state and can induce an M1 profile
The heme biosynthetic pathway and experimental porphyria models
miRNA-mediated control of Treg-cell development
Our proposed model of nsDNA-induced APOL1 expression through engagement of the cGAS/IFI16-STING pathway in human immortalized AB8/13 podocytes
A model summarizing the Aβ-induced actin cytoskeletal abnormalities via SHIP2-PI(3,4)P2-ARAP3-RhoA signaling pathway
The ovarian cancer pathway enriched by target genes of the identified miRNA biomarkers in IPA
The diagram shows butein inhibitory effect in TNF-Œ±-stimulated CCL2 expression at mRNA and protein level, attenuating IKBKE expression as a possible molecular mechanism in Caucasian cells; in addition to a possible signaling pathway for butein apoptotic effects in MDA-MB-231 and MDA-MB-468 TNBC cells
Complement system and therapeutic targets in bacterial meningitis
Schematic diagram showing role of Tbx15 on adipocyte browning and obesity
Docosahexaenoic acid (DHA) signaling pathway detected by GSEA
HDAC6 inhibition repressed B cell signaling pathways in NZB/NZW mice
The significant KEGG pathways enrichment of DEGs
The figure shows an MPR route that gets activated by the stimulation of progesterone receptor and has a role in cell proliferation by upregulation of PKA/cAMP by the activation of CREB/CREM/ATF-1
Possible mechanisms of actions of Rg1 in ER positive cells
Hypothetical schematic model for a novel oncogenic mechanism of G0S2
Synthesis of phosphatidylinositol and acyl chain remodelling
The signal PLC transduction pathway is coupled to PI re-synthesis to maintain the PIPn pool
The role of AKAP5 and AKAP12 in modulating oxidative stress in cardiac cells
The executable network model as seen in the BMA tool
Carcinoembryonic antigen‚Äêrelated cell adhesion molecule 1 (CEACAM1) as a central mediator of vascular aging
ROS‚Äêdependent priming and activation of the intrinsic cell death pathway
Pathway enrichment analysis of genes with eQTL associations with identified disease-associated SNPs
Network of pancreatic cancer-target genes
The different functions that As–RAD9 may be involved in
(A) Proteomic workflow for the investigation of molecular determinants o... (B) Protein interaction network including a subset of proteins identifie...
Influence of high CO2 concentration on hormone and stomatal regulation
Pathways controlling the epithelial-mesenchymal transition (EMT) program in prostate cancer (PC)
The Wnt signaling pathway and its regulation by ubiquitination The canonical Wnt signaling pathway is triggered by Wnt ligand binding to the complex of its receptor, Frizzled, and co-receptors LRP5/6
The TGF-β signaling pathway and its regulation by ubiqutination TGF-β released from the LTBP1 complex binds to TGF-β receptor II (TGF-βRII) and initiates transphosphorylation and activation of the associated TGF-β receptor I (TGF-βRI)
Notch signaling pathway by ubiqutination upon binding of Jagged/Delta (JAG/DLL) ligands to the Notch receptor (N1); the endocytic system is activated in the ligand-bearing cell
Possible mechanisms of hyperglycemia-induced cellular oxidative damage in the fetal heart
Dynamic mechanisms of inter- and intratumor heterogeneity
Strategies for therapeutic intervention of cancer involving FADD
Transforming growth factor (TGF)-β pathway in fibrotic liver which can lead to hepatocellular carcinoma
The complement and coagulation cascades signaling pathway and RT-qPCR verification
Effects of prototypical oncogenes and tumor suppressor genes on major metabolic processes
Crosstalk between RAS-ERK pathway and FOXM1
Mechanism of resistance to arsenic trioxide- all-trans retinoic acid (ATO-ATRA) therapy in APL
PTEN in cancer immune microenvironment regulation
Gene activities in the cytokine-cytokine receptor interaction pathway
Gene activities in the calcium signaling pathway
Gene activities in the TGF beta signaling pathway
Models of EGFR-ligand dependent pathway and EGFR-ligand independent pathway in EIS cells
(A) After co-culture between adipocytes and bre... (B) Interaction of adipocytes with BC cells inc... (C) Treatment with the anti-tumor compound shik...
Activation of CREM signaling pathway in spermatozoa of idiopathic infertile patients post-antioxidant treatment
Effect of Ad-Cyp8b1 on liver and intestine gene expression and mTORC1 signaling in HFD-fed mice
Parallel outline of several physiological roles of the TGFβ/p38, mitogen-activated protein kinase (MAPK), and P13k/AKT/mTOR signaling pathways
Targeted components of the MAPK and AKT signaling cascades by small-molecule inhibitors in cancer
Role of HO as master regulator of cell physiology
DNA-driven cGAS-cGAMP-STING signaling mediates innate immune response
DAMGO and morphine differentially assemble protein-interaction networks to control MOR spatiotemporal signaling
The TGF-beta signaling pathway annotated by ceRNA pairs of CDKN2B (p15)
In general, RA canonically binds to nuclear RARs to control the transcriptional expression of RA target genes
(A) Tyrosine is produced through an overproducing metabolically modified... (B) the newly introduced hydroxytyrosol (HT) pathway able to transform t...
Regulatory mechanism of the PI3K-AKT signal pathway in different groups
Regulatory mechanism of the MAPK signal pathway in different groups
Regulatory mechanism of the VEGF signal pathway in different groups
Molecular pathway linked to oxidative stress response in E
. Regulation of apoptotic signaling pathways through miRs by M. tuberculosis.
. Immunomodulation of macrophages through miRs.
A model for the non-autonomous regulation of ISC proliferation by enterocyte pyruvate metabolism
Overview of the components and regulatory factors in the complement alternative pathway (CAP)
Summary of natural product regulation in proteostasis machinery
Network of the glutathione metabolism pathway
MAPK signaling pathway: ERK1/2, JNK1/2, and p38
Model for leptin-induced EMT via Src and FAK signaling pathways
A putative model of a potato plant’s response to weak light and exogenous Ca2+
Model of the role of MyoF during skeletal muscle development
Canonical Wnt ligands induce two mutually exclusive Dvl2- and Fyn-dependent arms
Schematic diagram depicting the MAPK/ELK1 signaling pathway linking Ang II-RBM20-titin splicing
Proposed model for coordinated epigenetics regulation of ER isotype (ERŒ± and ERβ) expression dynamics in breast cancer
Hypothetical neuroimmune activation model leading to a vicious cycle of demyelination in metachromatic leukodystrophy (MLD)
Summary of SP600125 enhances C-2-induced cell death in bladder cancer cells through resisting JNK- SQSTM1/p62- Nrf2 mediated anti-apoptotic pathway and switching autophagy to apoptosis
The two faces of cGAS-STING signaling in cancer
Graphical summary of perceived crosstalk of BMP2-mediated signaling and the NO pathway
Signaling pathways involved in Epithelial-to-Mesenchymal Transition
A hypothetical scheme of the influence of ribosomal gene (RG) dosage in the genome of a non-carrier (green text and arrows) and a carrier (red text and arrows) of a monogenic autism mutation on the disease severity
Transcription regulators (TRs) that modulate glycolytic metabolism in cancer cells
Overview of the cell structure and function
Diagram that illustrates the in situ flow of downregulated proteins (mark in green) in early development as a consequence of cAMP stimulation
Main TLR-mediated signaling pathways triggered upon stimulation by LPS and LPG
Discovery of metabolic pathway identified in both optimal cutting temperature-embedded and formalin-fixed paraffin-embedded samples
Hypothetic model of signaling pathways involved in the differentiation of hiPSC-CM from mesodermal progenitors
Multiple immunosuppressive mechanisms coexist in tumor microenvironment
Schematic summary of the responses on energy metabolic pathway reprogramming by genotoxic or non-genotoxic hepatocarcinogens in rat liver cells
Hypothetical model to depict the role of Trpc1 channels in linking the inhibition of BMP pathway by noggin, and the activation of Cav1.2 channels in ectodermal cells
Schematic representation of hypothesized interactions between Smoothened and the CB1 receptor in the embryo
Continuation of the processes described in A
Reactive oxygen species (ROS) metabolism
Metabolic interplay between various ROS generators
Intracellular molecular alterations and their effects on tumour microenvironment immune activity
Scheme of chorismate synthesis from aromatic amino acids (tyrosine and phenylalanine) or the shikimate pathway
Model of DON toxicity to bovine renal epithelial cells
The Wnt/β-catenin signal transduction pathway in homeostasis
Schematic diagram of mRNA-miRNA interactions associated with the vascular endothelial growth factor (VEGF) signaling pathway
Aristolochic acid-induced cancer behavior in SV-HUC-1 cells
Schematic of nicotine-mediated signaling pathway with the stimulation of (α7)5 nicotine acetylcholine receptor (nAchR) and (α4)2(β2)3 nAchR
Mechanisms involved in activation and regulation of NLRP3 canonical pathway
Gene expression levels of central carbon metabolic pathways
Possible mechanisms of ERβ-induced apoptosis in tumor cells
Possible mechanisms of ERβ-induced autophagy in tumor cells
NK cell features in chronic HBV infection
ST2/IL-33 immune cells signaling pathway
Simplified overview of the signaling pathways in the target cells presented in this review that are relevant for the development of a pharmacological therapy rationale
Working model of FH physiopathology and the effects of CoQ
MTX affects several signal transduction pathways implicated in the pathogenesis of rheumatoid arthritis (RA)
Schematic representation of the most common signaling pathways influenced by probiotic strains employed in C
Mouse models used to study the PI3K/AKT/mTOR axis in PCa
Mechanism of HER2 targeted drugs and EGFR family in breast cancer
NKG2D/NKG2DL interaction activates NK cells
Strategies for targeting the NKG2D/NKG2DL axis for cancer immunotherapy
Our model. PAK1 activates the PI3K/AKT signaling pathway and PKCŒπ activates PAK1 through Ect2 and RAC1.
Proposed hypericin biosynthetic pathway based on our metabolomics, transcriptomics and functional annotation (given in Table S6)
The inflammatory signaling pathway and the resulting downstream responses
A simplified diagram of estrogen signaling pathways, including genomic (canonical) and nongenomic (non-canonical) pathway
Schematic diagram of the proposed effects of ZnO nanocomposites on antigen-presenting cells and their potential role in inducing T cell responses in draining lymph node
Continuous impaired insulin signalling causes the activation of AD markers (GSK3β and TAU genes), thus increasing the amyloid beta aggregations leading to AD
The signaling pathways that regulate autophagy and autophagy-related proteins that are affected by astaxanthin (AST)
GREM1 expression is associated with genes involved in collagen formation and extracellular matrix (ECM) organization
Genes expressed specifically in the symbiont-housing gills of Loripes orbiculatus and putatively involved in symbiosis
Signaling pathway model of leptin in EA.hy926 endothelial cells
SPARCL1 interacts with BMP7, BMP7 acts on TGF-β pathway receptors, and activation pathway affects cell differentiation
Schematic diagram of the proposed mechanisms in SS MSG
Gut microbiota from colorectal cancer patients enhanced the progression of intestinal adenoma in Apcmin/+ mice
Biosynthesis gene cluster of gentamicin C complex and the predicted biosynthetic pathway of gentamicin B in M. echinospora CCTCC M 2018898.
Probing Kinase Activation in Patient-Derived Samples(A) Reorganization of kinase activities upon acquired BRAF inhibitor resistance in melanoma: matched melanoma cell lines were established from patient-derived xenografts (PDXs) from the same patient before and after acquired resistance to the BRAF inhibitor PLX-4720, giving rise to a model system comprising treatment naive, treatment sensitive, and treatment resistant cell lines
Pathways showing systemic immune dyshomeostasis and the effect of inflammatory trigger insults on cholinergic signaling in AD: the figure shows crosstalk among “trigger insults/inflammatory stimulus” i.e., polymicrobial infection, chronic stress, pro-inflammatory diet and cholinergic signaling to put forward the “Systemic Immune Dyshomeostasis” model as to connect the events leading to AD development and progression
Signaling pathways in osteoclast (OC) differentiation, survival and death
Main processes involved in exercise-induced and neurotrophin-mediated increased viability of dopaminergic neurons
Overview of canonical and non-canonical mammalian autophagy processes
Schematic showing the proposed dynamic changes in the localization of LHCGR, DENND1A.V2, and RAB5B in various cellular compartments
Effect of andrographolide and Simvastatin on the mevalonate pathway in HL-60 leukaemia cells
Ingenuity pathway analysis of the significantly altered miRNA found in the follicular fluid showing that 12 of these miRNA were related to the genes involved in the Organismal Injury and Abnormalities, Reproductive System Disease pathway
Ingenuity pathway analysis of the significantly altered miRNA found in the follicular fluid showing that 12 of these miRNA were related to the genes involved in the Inflammatory disease pathway
Proposed model depicting the underlying molecular mechanism by which aqueous bark extract of T
Schematic illustration of NLRP3 inflammasome pathway and potential blockade sites of various pharmacological inhibitors
Diagrammatic representation of known mechanisms of action of lithium in endocrine cancers
IL-22 signaling pathway for expression of acute phase response proteins
The ALDH1A1-retinoic acid-HIF-1Œ±-VEGF pathway is activated in breast cancer MCF-7 cells (A)
AMPK stimulates autophagy by phosphorylation of ULK1 at the Ser377 and Ser777
Coordinated contribution of ROS and BMPs to vascular diseases
Top 18 overlapping canonical pathways visualized as a network, which shows each pathway as a single “node” colored proportionally to the Fisher’s Exact Test p-value, where brighter red indicates higher significance
The top three molecular networks identified by Ingenuity Pathway Analysis (IPA)
Phosphoproteins identified in NIL-R (R) and NIL-S (S) roots inoculated with V. dahliae related to plant–pathogen interaction pathway in the KEGG database.
Different death mechanisms of liver cells are involved in the pathogenesis of liver injury induced by MNPs
KEGG pathway annotations of the PI3K-Akt pathway in non-small cell lung cancer
PI3K-AKT signaling pathway adapted from KEGG (ID: hsa04151) (A) the predicted targets and genes were signed in red; (B) the known targets and genes were signed in red
Schematic diagram of the mechanisms of action of miR-21 showing the regulation of the WNT signaling pathway in NAFLD mice
A control case interaction visualized on RPGeNet showing the connections between NRL, NR2E3 and CRX retinal transcription factors
Scheme illustrating the proposed mechanism by which ET-1 increases phenylephrine-induced contraction in hypertension and the effect of PPARγ activation
Injury-induced epithelial and interstitial Notch1 activity contributes to myofibroblastic phenotype and fibrosis
Epidermal growth factor receptor signaling pathways and common mutations associated with therapy resistance (A) and systemic approach for the identification and validation of therapy resistance targets as well as mathematical modeling and simulation of therapy response (B)
Pathogenesis of antibody‚Äêmediated rejection and potential therapeutic targets
The simplified lipid metabolic pathway in maize
Schematic representation of how ablation of IŒ∫BNS affects B cell activation and PC differentiation
Model of how PPM1H counteracts LRRK2 signaling pathway by dephosphorylating Rab proteins
Signal transduction pathways initiated by IL‚Äê29
Inhibition of leucocyte migration was included in early moderate exercise‚Äêmediated improvement of inflammation
Schematic diagram of resveratrol (Res)‚Äêmediated suppression of ALI through STAT3/SOCS3 signalling
Overview of pathways leading to IDO enzyme production and regulation
Various extra - or intracellular signals activates the RIPK3 protein directly or through RIPK1
Proposed mechanism of the anti-TGEV effect of Lp-1s
SPARC promotes the activation of the MAPK signaling pathway to increase the phosphorylation of ERK, JNK, p38, NF-Œ∫B and IKKβ, thereby accelerating the occurrence of HO in soft tissues and playing a role in the treatment of HO
On the one hand, several LncRNAs (green) regulate PKM2 expression via affecting cell signaling pathways (blue)
Part of the central carbon metabolism network (CCM) in Mtb
Comparison of central metabolic features of the Rifle comammox Nitrospira
The inhibitory effect of miRNAs on their target molecules in the UPS pathway
Highlighted NF-Kappa B Signaling KEGG Pathway (hsa04040) with Enriched Genes from the LRT Analysis (Bonferroni-adjusted p < 0.05) for Influenza Infected Subjects (–)
Highlighted NF-Kappa B Signaling KEGG Pathway (hsa04040) with Enriched Genes from the LRT Analysis (Bonferroni-adjusted p < 0.05) for Influenza Vaccinated Subjects (–)
Amyloidogenesis and the influence of lipid managing proteins
Proposed model for apoptosis suppression via R-Ras pathway by RasGRP2
Graphical abstract of how EGFR signaling pathway and downstream effector inhibit the miR-124a expression and the role of ETS2 in insulin production in pancreatic beta cells
CMTM7 activates Rab5 which controls the fusion of early endosomes and affects EGFR protein trafficking, an essential part of the PI3K/AKT signaling pathway
Study on the mechanism of the MPAPO promoting of corneal wound repair and axonal regeneration (A) MPAPO activates the c... (B) Schematic diagram of...
PH-EPS modulates the activation of RAW264.7 cells through the TLR4(Dectin-1)/NF-Œ∫B/MAPK pathway
Running young is more effective than running at midlife
The mechanism scheme uncovers that CRISPR/Cas9-mediated knockout of NSD1 promotes H3K27me3 methylation and inhibits Wnt10b transcription, thereby suppressing activation of the Wnt/β-catenin signaling pathway
Illustration representing the mechanisms of compound 1-induced human breast cancer cell apoptosis
Sperm structure and energy production mechanisms in the sperm cytoplasm and mitochondria
Antifracture pathways of potential targets for treating fracture from main active ingredients of Drynariae Rhizoma
Molecular pathway signaling of angiogenesis-induced epithelial-mesenchymal transition in hepatocellular carcinoma
Inhibitors and mutants of the histidine biosynthesis pathway
Schematic representation of the regulation of the expression of ZNF638 in response to thermogenic cues
Schematic presentation of TA on skin wound healing molecular mechanism
MicroRNA Regulatory network with miRs from the anti-survival/EMT group
A simplified scheme of core steroidal glycoalkaloid modification in tomato and potato species
Recognition of HSV-1 infection by pattern recognition receptors (PRRs)
The regulatory roles of lncRNAs in TAM polarization
Gene expression profiles of the PI3K-AKT signaling pathway in treated HepG2 cell
BRD4 is involved in the transforming growth factor β (TGF-ß)/SMAD signaling pathway
Schematic representation of the E-cadherin (E-cad) interactions and signaling pathway
Coexpression network was constructed by WGCNA
Schematic overview of androgen biosynthesis
TGF-β signaling pathway and its role in tumor immune microenvironment
A Simplified Version of the Canonical Wnt/ Beta-Catenin Pathway
Yellow-colored genes are up-regulated and blue-colored genes are down-regulated in COPD samples
MDC1 loss causes greater IR sensitivity than H2AX loss
Schematic overview of steroidogenesis and corresponding urine steroid metabolites
Schematic of basic metabolic pathways used in T cells
Redox regulation of apoptosis under ER stress
Redox regulation of IRE1Œ± to control UPR
Activation of the KEAP1-NRF2 and HSF1 pathways by electrophilic lipoxidation products
Warburg's theory that cancer cells depend on aerobic glycolysis led to the assumption that OXPHOS is downregulated in cancer
NLR-dependent regulation of MHC class I antigen presentation
The presence of the BRAFV600e mutation in cancer cells leads to an increase in cell proliferation, metastasis and patients mortality
Pathway analysis network of 131 preliminary potential genes
Antidepressant-like effects and mechanisms of GXDSF via mediation of the CaMKII-CREB-BDNF signalling pathway in chronic unpredictable mild stress (CUMS)-induced depressive rats
Schematic overview of the hypothesized molecular mechanism underlying of ES effects on lung cancer cells
p53 signaling pathway in LNCaP cells treated with LEP (1 × 10−6 M)
Apoptosis pathway in LNCaP cells treated with LEP (1 × 10−6 M)
Schematic of the potential role and mechanisms of icariin in HG-induced EPC dysfunction
Adaptive feedback signaling in BRAF V600E-mutated mCRC
Summary of altered metabolic pathways and regulatory mechanism of rFIP-nha against A549 cells
PrRP physiological functions and signaling—summary
The pathways activated by several dysregulated hormones in central obesity
(A) Estrogen biogenesis, and its metabolism. The male hormones, androste... (B) The signaling pathways initiated by estrogen interaction with its re...
Gut dysbiosis/permeability increase circulating LPS and exosomal HMGB1, leading to TLR activation in microglia and the induction of iNOS and superoxide
Signaling pathways and therapeutic targets
IPA® analysis of signalling pathways of the genes differentially expressed upon lysozyme treatment
SPRY-altered signaling network profiles in mammary stromal fibroblasts
The HCC microenvironment inhibits SIRT4 expression in TAMs and modulates alternative activation of TAMs, which contributes to HCC development
Toll-like receptors (TLRs) in Lamellibrachia luymesi
(A–C) The most significance predictive genes for renal ischemia-reperfusion injury (IRI) in the rat model
Metabolic pathway of n-alkanes and the enzymes implicated in oxidation and hydroxylation processes in Y
Conflicting roles of RASAL2 in different cancers
Proposed mechanism of pancreatic cancer cell proliferative arrest caused by PTP1B inhibition
PPI network, pathway crosstalk and gene-pathway analyses of the DEGs from the GSE9116 dataset
IRAK1 kinase drives distinct prosurvival responses to microbial infection and ionizing radiation
Schematic representation of mechanism of miR21 in PC development
A summary diagram demonstrating the contribution of IGF-1/IGFBP to transcriptional levels of PPAR-γ, VEGF, and HIF-1Œ± under the administration of BV intervention
a Hypothesis and Summary—Monocytes and macrophages respond differentially to statin
Overview of YAP regulation by mechanical stimuli
YAP regulation by focal adhesion signaling
Non small cell lung cancer pathway circuit
Non small cell lung cancer pathway logic circuit with miRNA
The RAS-ERK signaling pathway and associated disorders
Glycolysis and biosynthetic pathways emanating from glycolysis
Gluconeogenesis pathway in glucose deprived lung cancer cells
Functional enrichment analysis and construction of PPI network
Schematic presentation of the signaling pathways involved in resistin-induced angiogenesis in human osteosarcoma cells
The lncRNA HOXA11-AS recruits DNMT1 to the promoter region of HOXA11, causing its methylation and subsequently resulting in suppression of HOXA11 expression and activation of the Wnt signaling pathway, which ultimately promotes stem cell characteristics in hepatocellular carcinoma
LKB1-proficient tumors display coordinated control of metabolism, DNA repair, and mitochondrial dynamics
STRING analysis of integrin signaling pathways and response to wound healing pathways
Cross talk between induction of mitochondrial oxidative/nitrosative stress and autophagy
(A) The JAK-Stat signalling pathway. (B) Cytokine signally through JAK/Stat combination.Upon binding to a cyt...
Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of the target genes of CTD-2357A8.3 in HNSCC tissues
The canonical WNT/β-catenin pathway: “on” and “off” states
WNT/β-catenin, TGF-β1, PI3K-AKT, SMAD, and PPARγ pathways
Canonical WNT/β-catenin pathway, Warburg glycolysis, and cancer
Schematic view of microglial activation and cross-talks between microglia and other immune factors in the pathogenesis of Parkinson’s disease
Reaction fluxes for (A) scenario 1 (Functional GLOI), and (B) scenario 2 (Non-functional GLOI)
Schematic representation of the endocytosis pathway
MyD88-dependent and TRIF-dependent TLR signaling pathways
Proposed model for the role of TLR-mediated innate immune events in regulating the Th1/Th17 and Th2 immune balance
Predicted localization of proteins and biosynthetic pathways in Synechocystis
FGFR pathway.FGFRs dimerize upon ligand building and trigger a downstream cascade of signaling pathways
Astaxanthin improves insulin sensitivity and glucose uptake
Disease-associated enzymes involving TNF and IL-1 pathways leading to NF-Œ∫B activationRed proteins are involved in TNF and blue in IL-1 signalling
Construction of pathway map and PPI interaction map
Conserved and novel homologues of bilaterian genes involved in axis patterning and regulated by the Wnt/β-catenin signalling pathway in Hydra
A: schematic of the components of the integrate... B: regulatory network representing 6 signaling... C: metabolic pathways coded in the metabolic si...
Aim2 protein-mediated modulation of AD-related inflammation
Schematic diagram showing molecular mechanism of varicocele-induced testicular dysfunction and its prevention by MAS
The Coral2 module-based phosphatidylinositol (PI) signaling system networks
The role of insulin signaling and insulin resistance in MetS and skin diseases
Chronic inflammation in MetS and skin diseases
Schematic representation of NLRC5’s role in renal diseases
(A) Mechanism VI: The macrophages from peritoneum, lung, liver, and spleen upregulate more trained immunity (innate immune memory)-related metabolic genes than that of adipose tissues, and the macrophages from peritoneum, small intestine, and adipose tissues upregulate more trained immunity-related metabolic genes than bone marrow macrophages (For detailed expression data, see )
Biosynthetic Pathway of Camalexin and Related Metabolites.Enzymes are marked in red, detected compounds are labeled in blue, and biosynthetic intermediates in black
Models of [14C]Acetate Pulse-Chase Labeling of MGDG Synthesis in act1 and act1 lpcat1 lpcat2 Leaves.The models indicate the relative rate of labeled fatty acid flux through the eukaryotic pathway of MGDG synthesis within the pulse-chase experiment
Molecular mechanisms of p53 loss of heterozygosity in breast cancer in response to DNA damage
Proposed mechanisms for the role of MC mediators in response to tumor cells
(A) The fungal cell wall and the targets that have been explored for antifungal development: β-D-glucan synthase, chitin synthase, and the enzyme Gwt1 from the GPI anchor pathway; (B) Echinocandin exposure causes cell wall stress by inhibition of the β-D-glucan synthase
Model of the Action circTTN Competitively Sponging miR-432 Mediating Myoblast Proliferation and Differentiation
Cellular context of TLR5 engagement by UPEC FliC in the bladder leading to early IL-10 induction
Anthocyanin biosynthetic pathway and expression of related genes during bract development in poinsettia varieties
PI3K-Akt signaling pathway changed in FSH-positive relative to negative NFPAs
The most significant module of PPI network of DEPs involved in ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway
LPS, lipopolysaccharide; TLR4, toll-like receptor 4; iNOS, nitric oxide synthase; NF-ƒ∏B, nuclear factor kappa B; CBP, CREB-binding protein; IRF-1, interferon regulatory factor 1; AP-1, activator protein 1; STAT1, Signal transducer and activator of transcription 1; Iƒ∏-B, inhibitor of kappa B; TRAF6, tumor necrosis factor receptor-associated factor 6; CD14, cluster of differentiation 14; LY96, lymphocyte antigen 96; IRAK, interleukin-1 receptor-associated kinase; MYD88, myeloid differentiation primary response 88; TAB1, transforming growth factor-beta-activated kinase 1-binding protein 1; p38MAPK, mitogen activated protein kinase p38; IFNγ, interferon gamma; JAK, Janus kinase; CALM, clathrin assembly lymphoid myeloid leukemia; NO, nitric oxide
The probable mechanisms of action of IGFBP-2 in the CNS
Network visualization of pathways enriched with genes influencing platinum-based treatment response in oral cancer.Hexagon shapes are genes
Network visualization of pathways enriched with genes influencing non-platinum-based treatment response in oral cancer.Hexagon shapes are genes
Tobacco-smoking associated genes map to interconnected interferon and stress response signaling networks
Proteins and metabolites in JK1 that change by >2-fold relative to wild-type E
Neutrophil immunometabolism in cystic fibrosis
Scheme of the mechanisms in the protective effect of nerolidol on LPS-induced ALI
The mTOR signaling pathway is involved in liver IR injury and plays crucial roles in autophagy
Proposed schematic diagram of LPS-induced ROS-mediated neuroinflammation, neurodegeneration, and memory deficits via dysregulation of the JNK/NF-Œ∫B/Akt signaling pathway
(A) Module 1; (B) the enriched pathways of module 1; (C) module 2; (D) the enriched pathways of module 2; (E) module 3; (F) the enriched pathways of module 3
. Differential whole transcriptome assay where stars denote genes up-regulated by tumor necrosis factor-Œ± (TNFŒ±) (40 ng/ml) and downregulated by apigenin (40 ŒºM).
. Differential whole transcriptome assay highlighting genes in MDA-MB-231 cells up-regulated by tumor necrosis factor-Œ± (TNFŒ±; 40 ng/ml) and down-regulated by apigenin (40 ŒºM).
. Analysis of protein–protein interaction (PPI) by online bioinformatics.
. The signaling events involving geminin, RA signaling and pluripotency factors.
Schematic diagram of the effects of hydrostatin-SN10 on the JAK2/STAT3 signaling pathway
Diagrammatic representations of putative mechanisms of microRNA 375 in regulating metadherin-induced cell proliferation, cell migration, and angiogenesis in human colorectal cancer
Comparison of HTRgene results to known biological pathways for cold and heat stress
PLNet2: LocPL pathway reconstructions (first 100 paths)
Protein–protein interaction network of the differentially expressed proteins between IH-exposed HUVECs treated with or without estradiol (E2)
Ezrin is known to promote cancer progression through various molecular mechanisms, as highlighted in the signaling insets
Two‚Äêsignal model of inflammasome signaling
Main signalling pathways of programmed necrosis in cardiomyocytes
Biochemical pathway showing the interplay between different actors in DAG and phosphatidic acid signaling
Biochemical pathway in neutrophils showing the signaling cascade and the effects related to DAG and PA activation
TSC2 mediated crosstalk between the Akt/mTOR pathway and the cyclin D1-CDK4/6 axis.The cyclinD1/CDK4/6 axis is responsible for increased phosphorylation TSC2 and TSC1, and promotes the phosphorylation of the mTOR substrates, 4E-BP1 and S6K1
Infectious lung disease and autophagy pathway
Pulmonary arterial hypertension and autophagy pathway
The agonist (e.g., acetylcholine, carbachol, pilocarpine, etc.)
The agonist (e.g., epinephrine, norepinephrine) binds adrenergic receptors
The agonist (e.g., serotonin) binds serotonin receptors
The agonist (e.g., dopamine) binds dopamine receptors
The agonist (e.g., bradykinin) binds bradykinin receptors
Agonist (e.g., histamine) binds histamine receptors
Agonist (e.g., chemokines) binds chemokine receptors, that either couple the PLC signaling pathway with a stimulatory effect (+) that triggers intracellular calcium release (↑ Ca2+), or couple the AC signaling pathway with an inhibitory effect (-) that induces cAMP decrease (↓ cAMP), or couple the PI3K signaling pathway stimulating MAPK
Extracellular and intracellular (canonical and non-canonical) adenosinergic pathways
Effects of extracellular ADO on subsets of macrophages
The cellular effects of extracellular ADO in the regulation of lymphocyte functions
Cell signaling pathways activated in osteogenesis and angiogenesis models: Wingless-related integration site (Wnt) pathway, bone morphogenetic protein (BMP) pathway, and fibroblast growth factor (FGF)/platelet-derived growth factor (PDGF) pathway
Canonical pathway explaining the NASH progression from steatosis to hepatocellular carcinoma
Schematic diagram showing molecular mechanism of SC in varicocele-induced testicular dysfunction in male SD rats
The roles of non-canonical Wnt pathways in osteoclast differentiation and function
The canonical KEAP1/NFE2L2 antioxidant signalling pathway, induced by electrophilic ligands
Schematic of DUBs and their role in Hippo signaling
Signaling pathway with involvement of RASSF1A
The Notch, PI3K, TGF-β, Wnt/B-catenin, and EGFR/Ras signaling pathways are interacting with each other
Altered cancer pathways in ASL, CCA and HCC
Caffeine, theanine and catechin biosynthetic pathways in plants, and expression patterns of genes related to quality metabolites in ‘Xiaoxueya’ leaves
Summary of changes to the Wnt pathway as a result of AD + TS treatment
Defective proteasomes in CANDLE/PRAAS subjects provoke ER stress and trigger the so-called unfolded protein response (UPR) which is associated with inflammation
Mutant proteasomes from CANDLE/PRAAS subjects have a potential pro-inflammatory potential due to the negative impact they exert on mTORC1
Schematic representation of the proposed mechanism by which T
Signal transduction pathways in KEGG pathway analysis
Nervous system pathways in KEGG pathway analysis
Immune system pathways in KEGG pathway analysis
A number of studies suggest that an increase in microbial BSH activity results in a reduction in stimulation of intestinal FXR
Major phospholipid biosynthetic pathways, genes involved, and subcellular localization of the encoded enzymes.PTDSS1,PCYT1A, andPISD from this study (all in red font) are associated with syndromic skeletal dysplasias
Representative model of the MMP-2 and MMP-9 secretion induced by leptin in a cultured model for breast cancer
Models for CAN function in larval development
Metabolic pathway of DEGs related to lipid metabolism in the liver by DNA microarray analysis
Schematic view of the Wnt signaling pathways between MSCs and HCC cells in inflammation microenvironment
Schematic view of the TLR4 signaling pathways between MSCs and HCC cells in inflammation microenvironment
Schematic view of the AP-1 and PKB signaling pathways between MSCs and HCC cells in inflammation microenvironment
SKA3 influences cell proliferation and apoptosis in LM3 and Huh7 cells via P53 signaling pathway
(A) Apoptosis adapted from KEGG (ID: hsa04210), the know targets were signed in red; (B,C) the insulin signaling pathway adapted from KEGG (ID: hsa04910) the predicted targets and other human proteins were signed in red
Hormone-related pathways enriched in DEGs of the brain and gonads
The adaptive divergence of Notch signalling pathway in tiger
As a tumor-suppressor gene, RASSF1A mainly acts as a crossroad of three intertwined molecular signaling mechanisms including Ras/Rho GTPases, MTs, and Hippo pathway
Several typical post-translational modifications of PGK1
Illustration of the NEK2/β-catenin/Myc/KDM5B/H3K4me3 pathway
Regenerative abilities contribute to the application of BM-MSC in psychocardiological disease
Schematic overview of the WNT signaling pathway
Schematic of the proposed pathway of IPs synthesis
Schematic diagram of the main production and uptake mechanism of exosomes
TGF-β1 effects on the balance between the canonical WNT/β-catenin pathway and PPARγ
Interactions of TGF-β pathways, WNT, Smad and the Hippo pathway in fibrosis
Model of multistep regulation of autophagy by TRPML1
Biomechanical stress stimulates the mechanosensitive molecules on the EPC surface, and then induces cytoskeleton rearrangement and activates series of downstream signaling pathway
Small molecules guiding mesenchymal stem cell osteogenic cell fate determination
LRF/ZBTB7A’s silencing compromises Warburg effect and induces apoptosis in cancer cells
Schematic presentation of positive and negative regulators of RLRs (Top) and melanoma differentiation-associated protein-5 (MDA5) (Bottom) through PTMs or non-PTMs and immune invasion viral proteins interacting with RIG-I (Top) and MDA5 (Bottom)
Schematic presentation of positive and negative regulators of cGAS through PTMs or non-PTMs and immune invasion viral proteins interacting with cGAS
The primary targets of lithium in the cell are the glycogen synthase kinase 3/A (Gsk3/A) and inositol trisphosphate (InsP3) signalling pathways
Schematic model of insulin-stimulated glucose uptake in adipocytes
Following genotoxic stress, such as ionizing radiation, increased levels of cyclin E and the associated kinase activity are responsible for phosphorylating a critical cellular target implicated in apoptosis
A model of signaling pathway from oncogenic H-Ras to increased cell proliferation and transformation
Model for GalR1 neuroplasticity within the LC
Soluble phospholipid precursors: (G-6-P, glucose-6-phosphate; I-3-P, inositol-3-phosphate; C-P, choline phosphate; CDP-C, cytidinediphosphate choline)
In the current study, we have demonstrated that TGF-β1 induces rapid activation of p38 MAPK followed by a more delayed activation of the PKB/Akt pathway in lung mesenchymal cells/fibroblasts
Working model for the effects of 15d-PGJ2 and thiazolidinediones on TNF-stimulated NFŒ∫B activation and COX2 expression
Potential sites of action for reactive oxygen species in the regulation of the insulin signaling pathway
Bioinformatic network representing the core signaling pathway downstream from V2R occupation in IMCD demonstrated by previous studies (labeled in grey) and the five proteins regulated in response to long-term dDAVP administration that were validated by immunoblotting in this study (labeled in red)
(A). Proposed model for mXinα localization at the adherens junction of t... (B). β-catenin plays a central role in regulating Wnt signaling and the...
LTCCs are voltage-gated Ca2+ channels that form heteromeric complexes on the neuronal membrane and are composed of a voltage-sensitive Ca2+ pore forming Cav or α1 subunit and auxiliary β, α2δ and γ subunits (, )
Regulation of ROS-mediated activation of the p38 MAPK stress response signaling pathway
Mechanisms of bile acid and cytokine inhibition of CYP7A1 gene transcription
In the canonical pathway (left), stimulation of TNF receptors (TNFR), IL-1 receptors (IL-1R) or Toll-like receptors (TLR) with their cognate ligands activates TRAF proteins and subsequently the kinase TAK1, which phosphorylates and activates IKKβ
Stimulation of IL-1R or TLR leads to the recruitment of MyD88, IRAK and TRAF6 to the receptor complex
Polyubiquitination by TRAF2 and TRAF6 not only mediates signaling by TNFR, IL1R and TLR (see ) in the innate immunity pathways, but also plays an important role in adaptive immune responses by activating IKK in response to stimulation of TCR
The intrinsic apoptotic signaling pathway
The extrinsic apoptotic signaling pathway
The temporal dynamics of signalling networks is described by                         ordinary differential equations, which are known as chemical kinetics                             equations and are derived                         similarly to the Michaelis-Menten equation, familiar to any biologist
Aspects of PRLR signaling as related to mammary gland function
Potential models to describe how Ras/PKA signaling activity influences autophagy and how this control might be coordinated with that of the Tor signaling pathway
A pathway (shown by the transparent shapes) involving the activation of the Gs/adenylyl cyclase/cAMP signaling cascade seems to be prominently involved in the LHR-provoked phosphorylation of ERK1/2 in MA-10 cells
A proposed model for PMT action on Gq-mediated mitogenic signaling
Schematic representation of stress-induced release of eHsp72
Synthesis and breakdown of proteins by amino acids
Telomeric and nontelomeric signals induce senescence via tumor suppressor pathways in human and mouse cellsInduction of p21 and p16 by senescence-inducing signals results in inhibition of activity of CDK2 and CDK4/6
Schematic diagram of some signaling pathways that could mediate long-term                         changes in cellular plasticity as a function of sexual experience
Heterogeneity of Pacemaking Ability among SCN Neurons Robust rhythm generation in SCN neurons is thought to rely on circadian expression of Period (Per1, 2), Cryptochrome (Cry1, 2), Rev-Erb, Ror, and Bmal1 genes, and constitutive expression of Clock
Schematic of Thy-1-associated signaling pathways
Schematic depicting the effect of the PI3-K/Akt pathway and the JNK pathway on Bad activation in the peripheral area after brain ischemia/reperfusion injury and pharmacological manipulation
Selected cytokines and their signal transduction pathways are depicted in simplified fashion to illustrate representative interactions between cytokine and glucocorticoid receptor (GR) signaling events
Model of combinatorial signalling by TGF-β1 of the inducible activation of FAK and AKT in anoikis-resistant myofibroblasts
RGC death induced by glaucomatous stimuli involves receptor-mediated caspase activation, and caspase-dependent and -independent components of the mitochondrial cell death pathway
A diagrammatic representation of insulin on growth factor signaling through the Ras-Raf, MEK-ERK signaling pathway with downstream effects on gene transcription through ERK translocation
Insulin-mediated activation of PI3K signaling pathways
A diagram showing several factors involved in lens development
Regulation of induction and vesicle nucleation
(A) The strategy for identifying Ub modification sites in protein target... (B) Measurement of the abundance of Ub linkages by the AQUA strategy usi...
Apoptotic signaling pathways as seen through death receptor ligation of TNFR or Fas (extrinsic signaling, type I cells) or through activation of the mitochondrial pathway through Bcl-2 family members (intrinsic signaling, type II cells)
A schematic illustration of the principal signaling pathways that are affected by sodium arsenite (As) treatment
During tubulogenesis in the MDCK cells, HGF binds to the CMET receptor tyrosine kinase receptor and activates the ERK/MAPK pathway, which leads to transcription and secretion of tubulogenic fibronectin
Drugs that regulate hepatic bile acid and other organic solute uptake, synthesis, detoxification and secretion
Proposed model for the activation of oligodendrocyte apoptosis by MHV infection
Proposed extracellular ATP involvement in corneal epithelial wound healing that summarizes the pathway from ATP release caused by cell injury to wound closure, including P2Y activation, intracellular Ca2+ release and EGFR signaling
Signaling pathways downstream of adiponectin in cells of the cardiovascular system
Intracellular signaling cascades activated by BDNF-stimulated autophosphorylation of TrkB receptors may affect prominent pathways responsible for elevations of intracellular Ca2+ levels in neurons
Schematic of rPMT signaling pathways in cardiomyocytes
In the setting of cerebral ischemia, excess intracellular calcium (Cai2+) activates various lipases, including phospholipase A2 (PLA2) and phospholipase C (PLC) which breakdown both intracellular and membrane phospholipids and release arachidonic acid (AA)
6-OHDA treatment results in cytoplasmic accumulation of pCREB accompanied by repression of CRE-mediated transcription and decreased expression of BDNF and Bcl-2
Pathways for the synthesis of the major phospholipids in S
Fibrillar Aβ binds to integrin and activates FA signaling pathway to regulate cell cycle through different pathways including MAPK, PI3-K, and GSK-3β kinases (see text for details)
Schematic illustration of anti-apoptotic pro-survival signaling mechanisms, termed the reperfusion injury salvage kinase (RISK) pathway, that have been proposed to protect the heart from reperfusion injury
TGFβ has been shown to be an important regulator of many of the processus leading to tubulointerstitial fibrosis including EMT, cellular infiltration and apoptosis leading to tubular atrophy and interstitial accumulation of extracellular matrix proteins
Scheme depicting a molecular pathway by which cell-cycle-related molecules promote cell death in neurons in development and disease
Stimulation of H3R on sympathetic nerve endings results in the Gβγi-mediated intraneuronal activation of the MAPK cascade
Inhibition of COX-2 modulates multiple functional pathways during acute inflammation and pain
Schematic representation showing the plausible signaling events from uPAR integrin complex
Glutamine/Glutamate (GLN/GLU) cycle in neurons and astrocytes
A schematic drawing outlining the main signaling pathways activated in response to ligand engagement with the GLP-1R and their major downstream effects on acute insulin secretion, insulin synthesis, preservation of β cell function and mass and regulation of proliferation
Schema outlining the signaling mechanisms reported to be involved in GLP-1R-induced differentiation/neogenesis of pancreatic precursor cells, proliferation and in the prevention of apoptosis
Signaling during SMC phenotype switching
Apoptotic signaling during SMC response to injury
Highlighted in the figure is the TLR4 initiated and AC-3, cAMP, and PKA dependent signaling pathway that dissects with and abrogates the lipid raft mediated endocytic pathway
LH binds to the LH receptor, stimulating the mobilization of stimulatory guanine-nucleotide binding proteins (GsŒ±)
Binding of GnRH to the GnRHR triggers an intracellular signaling cascade, which radiates from activation of PKC
SDF binding to CXCR4 leads to the activation of multiple G protein-dependent signaling pathways, resulting in diverse biological outcomes such as migration, adhesion, and transcriptional activation
1. The proteasomal degradative pathway and ER quality control mechanisms are closely coupled.
How both apoptotic death and immunity may be triggered by dsRNA
The oval of iNOS-inducing signaling pathways
Blocks of iNOS-blocking signaling pathways
Signaling mechanisms for the activation of HAT and HDAC
Akt has been described to inhibit apoptosis at multiple levels: signaling pathways, transcription factors, and, in the intrinsic pathway of PCD, at pre-mitochondrial, mitochondrial, and post-mitochondrial levels
By surveying the literature on the function of each of the 20 gene products that were most dramatically changed in RSV transformed CEFs, we propose a model of their concerted action of promoting cellular transformation and tumor progression
Hypothetical role of Hsp72 in the regulation of oxidative stress-induced HMGB1 cytoplasmic translocation and release
The figure summarizes effects of P450 inhibitors (both the non-specific inhibitors Metyr and SKF-525A and the CYP2E1-selective inhibitors CHX and DITC), P450 inducers (PYR, CLO), GSH depletors (BSO, DEM), and intracellular GSH enhancers (GSH for kidney cells and Met for hepatocytes) on metabolism and acute cytotoxicity of Tri
MiR-103/107 and PANKs may constitute coordinated transcription units with synergistic cellular effects concerning cellular acetyl-CoA levels and other metabolic pathway elements
Regulation of cell proliferation and cell death by PKCŒµ
PrPC may inhibit Bax-mediated apoptotic pathways at several different points, either by a direct interaction between the two proteins or by involvement of additional, intermediary proteins
Putative vasoactive signaling pathways involved in neurovascular coupling
The role of ZIP1 expression and zinc accumulation in the pathway and bioenergetics of citrate production and citrate oxidation in normal versus malignant prostate cells
Representation of the dual effects of zinc in Bax-associated induction of mitochondrial apoptogenesis in malignant prostate cells
Interaction map of the Notch signaling pathway
The figure depicts several types of signaling thought to occur from endosomes, as discussed in the text
Hypothetical model of ischemic/hypoxic effects on cardiac myocytes and stem cells
(A) Adenylyl cyclases are targets of multiple r... (B) The β-type phosphoinositide-specific phosph... (C) Example of cross talk from the Gq (GqŒ±), G...
illustrates the possible mechanisms that underlie VIP’s actions in SCN neurons
Function of JNK/SAPK scaffolds in organizing the MKKK-MKK4/MKK7- JNK signaling module
Oxidative stress initiates a cascade of reactions leading to cell death via one or more sequences of molecular events
The upper panel depicts PTH-activated survival pathways, and the negative feedback on these pathways caused by stimulation of Runx2 degradation
Schematic diagram showing the major components that control [Ca2+]i in myometrium
Proliferation induced by androgen independent pathways
Nitrite may be reduced to NO by a variety of metal containing enzyme systems and the NO or the NO-modified proteins and lipids may in turn mediate cytoprotection against IR injury through any a variety of mechanisms
GenMapp pathway showing the impact of 1 week of STZ-DM on transcription in pathways related to cytokines and the inflammatory response
Binding of ligands to CD36 leads to cell specific activation of signaling pathways and responses
The differential stimulation of the units of the receptor heteromers determines the predominant signalling pathway and the consequent changes in neuronal excitability and gene transcription, with implications for plastic changes in the glutamatergic synapse, such as phosphorylation and recruitment of AMPA receptors (AMPARs) to the postsynaptic density
Binding of IL-7 causes dimerization of its receptor chains and activation of the receptor–associated JAK1 and JAK3
Newly synthesized GLUT4 traffic through a GGA-dependent and trans-Golgi Network (TGN) sorting into the insulin-responsive storage compartment (IRC)
The mTOR pathway responds to growth factors via the class I PI3K pathway
The binding of an inflammatory stimulus, such as the bacterial endotoxin lipopolysaccharide (LPS), to the membrane-bound CD14-toll like receptor (TLR) complex in inflammatory cells (i.e., macrophage, microglia and dendritic cells) results in the stimulation of two different pathways involved in the transcription activation of several inflammatory mediators: nuclear factor-Œ∫B (NFŒ∫B) and a mitogen-activated protein kinase (MAPK) cascade.
5-HT2A receptor agonists cause activation of GŒ±q/11 proteins which in turn activate the second messenger enzyme PLC
This model shows how GDNF can promote cell cycle progression via activation of Src kinase(s) and a PI3K/Akt pathway to increase N-myc gene expression
Summary of known actions of activated ras-p21 in cells, beginning (top, left) when a growth factor binds to its cell receptor
A diagram indicating the simulation of the Map Kinase pathway under stimulation by EGF only (black starred line), Bacterial load only (red circled line) and both (blue triangled line)
A: Networks of pathways unique in the HIV-1 regulated mPBMCs. The networ... B: Relationship networks of genes associated with the NK cell signaling...
The genes with inactivating abnormalities; TRAF2, TRAF3, cIAP1, cIAP2, and CYLD, are indicated by green objects while the genes with activating abnormalities; LTBR, TACI, CD40, NIK, and NFKB2, are indicated by red objects
VIP acting through the VPAC1/2/ receptors activates adenylate cyclase resulting in the activation of PKA
The respective balance between Gi- and Gs-dependent signalling pathways and their roles in the modification of FcŒ±RI-mediated mast cell degranulation
Upper panel illustrated ligand-induced conformational change followed by dimerization progressing from Panels A to C (see Jorissen et al
A & A1, clathrin-independent caveolar endocytosis; B, clathrin-independent non-caveolar (lipid rafts) endocytosis; C, clathrin-dependent endocytosis; D, plasma membrane to LE/lysosomes to TGN pathway
ST/SLT upon binding Gb3 can enter the cell by clathrin-dependent endocytosis, and also by clathrin-independent mechanism from lipid rich, plasma membrane microdomains (lipid rafts)
FGF binding to the outside of FGFR induces FGFR dimerization, receptor autophosphorylation followed by phosphorylation of the lipid-anchored docking protein Frs2Œ±
(A) Gene regulated by Pax6 in the prospective l... (B) Three genes, c-Maf, Prox1 and Pitx3, are di... (C) A complex regulatory network proposed to co...
Representative intracellular g-protein coupled signal transduction cascades
IGF-I leads to induction of multiple signaling intermediates down-stream of IGF-IR and IRS-1 ( □ )
Expression of genes contributing to the Immune Response (top) and Cell Cycle (bottom) GO processes at 4 wks of treatment (see  and 4) was visualized as networks using Pathway Studio software
A. Diagram showing the potential sites of modulation of the TGF-β signaling pathway by IL-1β or TNF-α in articular chondrocytes.
Two-step model of chordin gene regulation in the zebrafish gastrula
(a) cAMP dependent signaling, (b) PP2A dependent pathway, (c) IP3 and PKC dependent pathway, and (d) pathway for beta2 adrenergic receptor blockade
Activation of phospholipases (PLA2, PC-PLC, PI-PLC and PLD) following cerebral ischemia results in release of lipid second messengers 1,2-diacylglycerol (DAG), phosphatidic acid (PA), lyso-phosphatidic acid (lyso-PA), docosahexaenoic acid (DHA), and arachidonic acid (ArAc)
The two cell types are shown in the dashed rectangles as indicated
A. Schematic summary of the nitric oxide signaling system in HeLa cells.
Signaling mechanisms involved in lifespan regulation and the cellular response to genotoxic stress
Schematic diagram of a functional interacteome of all parietal cortex proteins identified to be significantly less oxidatively modified following the combined treatment of the enriched environment and antioxidant-fortified food (EA)
Models for the dual roles of KLF4 and KLF5 in tumor suppression and oncogenesis
a | In DNA vaccination, the plasmid DNA contains a fungal gene that is often under the control of an active promoter
Polarization of the EMS cell and the T cell in C
Nitric oxide (NO) is synthesized enzymatically from the amino acid l-arginine by three isoforms of NO synthase (NOS), including endothelial NOS (eNOS)
Peroxynitrite, formed from superoxide and NO, causes cell injury via lipid peroxidation, inactivation of enzymes and other proteins by oxidation and nitration and also activation of matrix metalloproteinases (MMPs) just to mention a few
Proposed role of the oxidative and nitrosative stress–poly(ADP-ribose) polymerase 1 (PARP-1) pathway in oxidant-induced cellular dysfunction and necrosis
Mechanisms of cardiovascular dysfunction in diabetes: role of superoxide and peroxynitrite
Schematic representation of signaling pathways that regulate Drosophila metabolism
*, denotes “activation” in response to Wnt3a
Multiple ERK scaffold regulate growth factor and adhesion signaling
Model of FAK FERM-mediated p53 turnover and cell survival
Upon TLR stimulation, the adaptor protein MyD88 is recruited to the receptor complex
The insulin signaling cascade branches into two main pathways
The Wnt-Frizzled signaling pathway employs Akt to regulate an array of vital cellular functions that involve cellular protection, angiogenesis, cardiovascular remodeling, DNA repair, and the maintenance of membrane asymmetry in neuronal and vascular systems
The Wnt-Frizzled signaling pathway regulates PS exposure and apoptosis
Schematic diagram of mitogen-activated protein kinase (MAPK) signaling and stimulating effects of peroxynitrite
Role of nitric oxide (NO) and peroxynitrite in cardiovascular pathophysiology
(A) Each Drosophila ovariole conta... (B) In the germarium, GSCs occupy... (C) Each cystoblast or cyst within... (D) The insulin pathway, which is...
The prototypical myelin-derived neurite growth inhibitors, their receptors and intracellular signaling pathway
A schematic illustration of NGF activation of KOR P2 during RA-induced neuronal differentiation of P19
Schematic presentation of the NF-Œ∫B signaling network in radiation-induced adaptive radioresistance
As described in the text, neuroprotective (in blue) and preconditioning (in green) mechanisms currently being explored for inhalational anesthetics in ischemic brain injury are depicted within the neurovascular unit
E2F target genes are regulated by repression of transcription in G0/G1 phase, followed by activation in G1/S phase
Many proteins regulate the activity of E2F and p53 in the apoptotic response
Putative signals which stimulate CECs to migrate include: chemotactic factors such as soluble VEGF secreted by RPE, contact between CECs and RPE, or contact with RPE extracellular matrix
Simplified schematic diagram showing putative regulation of B
GHS-R translocation to the leading edge of cells and ligation with exogenous or endogenously produced ghrelin result in release of intracellular calcium and PKC activation, causing an increase in actin polymerization along with Rac activation, thereby increasing cell motility
A proposed model to illustrate how the GSK-3β pathway coordinates with the Chk1 pathway to modulate Cdc25A levels during an unperturbed cell cycle, in response to DNA damage and in certain cancer cells
pDC have been demonstrated to respond to viral RNA and DNA through a unique molecular complex known as the “cytoplasmic transductional-transcriptional processor” (CTTP) (86)
TNF binding to TNFR1 stimulates two signaling complexes with opposing effects on cell survival
FIP200 functions to regulate diverse cellular processes, including cell proliferation, cell spreading, cell migration, cell growth and cell survival
(A) The Stat pathway. (B) The Smad pathway (C) The NFŒ∫B pathway. In unstimulated cells (A...
a | After fertilization, parallel arrays of cortical microtubules extend from the centriole and the large aster at the sperm entry point towards the dorsal side (where the plus end lies), and transport small membrane vesicles from the vegetal towards the dorsal animal pole
a | Chordin binds bone morphogenetic protein (BMP) through cysteine-rich domains CR1 and CR3
The extrinsic pathway is stimulated by UVB or binding of Fas ligand, tumor necrosis factor, or other cytokines to death receptors that results in activation of caspase-8
The two primary survival pathways involve activation of a mitogen-activated protein kinase (MAPK) cascade and activation of Akt
DNA replication and damage checkpoint regulation
RNA viruses are internalized through several mechanisms, either fusion with the plasma membrane or binding to a surface receptor (ACE2 for SARS-CoV, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) for MHV)
P. gingivalis impacts cell cycle control in GECs.
This schematic diagram illustrates proposed mER-mediated mechanisms that can mediate rapid estradiol-induced ERK1/2 activation
Binding of CXCL12 to CXCR4 activates multiple G-protein-mediated signaling pathways (such as PI3K, MAPKs and NFŒ∫B) and induces the release of intracellular Ca2+
Phosphorylation (P) of specific sites in PRs couple multiple receptor functions, including transcriptional synergy in the presence of steroid hormones and growth factors predicted to activate MAPK and/or CDK2, and nuclear import or export (shuttling) in response to MAPK activation
Triggering and amplification of the Wnt/β-catenin pathway in osteocytes in response to load
NEC pathophysiology is a complex series of events leading to a final common pathway of inflammation
Possible role of GPCR oligomerization in arrestin-mediated signaling
In response to EGF stimulation, Src phosphorylates RSK2 at Tyr-529 to facilitate recruitment of the inactive form of ERK to RSK2, which subsequently promotes the phosphorylation and activation of RSK2 by ERK when activated by EGF
Data in the current manuscript are consistent with normal interaction of IFN-Œ± and IFN-β with the heterodimeric IFN receptor at the cell surface
Model for BDNF enhancement of glutamate-induced phase shifting in the SCN, and potential locations in the signaling pathway where ethanol could inhibit this process
Involvement of IRAK-2, M, and 4 in the differential regulation of NFkB pathway
Androgen actions via intracellular androgen receptor mediated pathways
The description of the signaling pathway is in the text
Model for TGF-β1-induced PAI-1 expression in VSMC
Effects of p53 on the IGF-1 signaling pathway
Contractile agonists and mechanical signals activate proteins kinases (Abl, FAK, Src, MAP kinase, etc) and small GTPases (Rho, Cdc42 and Rac) that regulate the downstream effectors (CAS/CrkII, N-WASP, the Arp2/3 complex, profilin, paxillin/Hic-5, HSP27, cofilin, etc
Variation the insulin/insulin-like (IIS) pathway, including cross talk with target of rapamycin (TOR) signaling, is a possible explanation for the different life history syndromes of high and low pollen-hoarding strain bees
Model of progesterone-induced neuroprotective signaling
Catenins regulate downstream signals that impact on several aspects of cell behavior
Summary of the signaling pathways involved in hair follicle morphogenesis and regeneration
a, During development, basal epidermal cell density is low and cells proliferate
Metabolic pathway of lipid mediator production
Signaling and bipolar cell reprogramming
A putative transcriptional network that we have termed the “Diasporin Pathway” was constructed by applying the Occam’s Razor principle, i.e.
Viral sensing, following either direct fusion with the plasma membrane, or receptor-mediated endocytosis, initiates innate immunity and regulates virus-induced disease
(a) In the absence of Wnt signal, β-catenin forms a complex with Axin and APC
Working hypothesis on the mechanism by which plasminogen activator inhibitor-1 (PAI-1) causes hepatic steatosis
Two branches of TLR downstream signaling
We have previously demonstrated that butyrate induces colonocyte apoptosis via a non-mitochondrial, Fas-mediated, extrinsic pathway which is antagonized by activated Ras []
Cartoon of two of the most promising DNA repair pathways for cancer therapeutics
A representative schematic for the canonical and non-canonical pathways is shown
Wnt signaling begins with Frizzled (FZD) receptors resulting in the activation of Dishevelled (DVL) followed by the inhibition of glycogen synthase kinase (GSK-3β), Axin, and adenomatous polyposis coli (APC) tumor suppressor protein complex
A hypothetical scheme illustrates the putative intracellular signaling cascades serving as the context for the data collected in the current study
Signaling cascades initiated via TLR2- and TLR4-dependent activation
Model of the molecular pathways and their potential interactions involved during the development of the pyloric sphincter
Receptor tyrosine kinases (RTK) such as IGF-IR and EGFR, integrins, and G-protein coupled receptors (GPCR) can all stimulate PI3K
Several approaches can be employed when combining pathway inhibitors with other targeted therapies
D-Chip output was analyzed by Ingenuity to generate the diagram
(A) Intracellular pathways mediated by D1- and D2-class DA receptors. Ac... (B) Homologous desensitization process of GPCR. After ligand binding, GP...
Upon activation by receptor tyrosine kinases (RTK), PI3 Kinase which is comprised of a p85 regulatory and p110 catalytic domain converts PIP2 to PIP3
Potential interaction between two known Egr1 target genes, PTEN and fibronectin achieves a delicate balance between attachment and apoptosis of detached cells (anoikis)
Ginseng is able to improve glucose metabolism through multiple pathways: 1) Glucose disposal is increased partially due to activation of insulin signaling pathway and GLUT4 translocation by ginseng; 2) Ginseng is able to suppress food intake through inhibition of NPY expression in hypothalamus; 3) Physical activity is increased with ginseng through improvement of mood and psychophysical performance; 4) Fat composition and body weight are reduced partially related to up-regulation of thermogenesis and energy expenditure; 5) Antioxidant and anti-inflammation of ginseng may be involved in the mechanisms of insulin sensitization; 6) Ginseng protects islet function through antioxidant and inhibition of β cell apoptosis
Mechanism of berberine in regulation of metabolism: 1) Berberine enhances glucose uptake through induction of glycolysis, which is due to inhibition of aerobic respiratory; 2) AMPK activation stimulated by berberine is a consequence of inhibition of mitochondrial function; 3) Berberine suppresses adipogenesis through inhibition of PPARγ and C/EBPŒ± function; 4) Berberine is able to decrease intestinal glucose absorption by inhibition of Œ±-glucosidase; 5) Berberine up-regulates LDL receptor (LDLR) expression through increasing LDLR mRNA, which is related to inactivation of ERK and activation of JNK pathway
The classical and back-door pathways of androgen biosynthesis
Glucose provides cells with a source of Ac-CoA for fatty acid synthesis (blue arrows), which is enhanced in tumors due to oncogene-driven expression of the lipogenic enzymes ATP-citrate lyase (ACL), acetyl-CoA carboxylase-1 (ACC) and fatty acid synthase (FAS)
Small integrin-binding ligand N-linked glycoproteins (SIBLINGs; bone sialoprotein (BSP), dentin matrix protein 1 (DMP1) and osteopontin (OPN) are shown) can initiate Arg–Gly–Asp (RGD)-dependent and RGD-independent interactions with several integrins (such as αvβ3 and a9β1, respectively)
The schematic diagram demonstrates intracellular signaling events in the Ras/ERK1/2 pathway as well as the downstream cascades activated by GDNF in spermatogonial stem cells
Multiple Pathways of TIMP-1-CD63 signaling
This model shows the interactions between the components of some of the major pathways that affect AQP2, and summarizes most of the points outlined in this review
In wild type flies, the combined action of the prepattern genes and signalling through the Wingless pathway leads to the expression of proneural genes of the achaete-scute complex in small groups of cells
The achaete-scute expression is initiated by the combined action of the prepattern genes
Flow diagram illustrating 14-3-3/Bad interaction
Four hyperglycemia-related mechanisms may promote diabetic atherosclerosis: 1
Upon initiation of the IPC stimulus, endogenous triggers such as adenosine, opioids, and bradykinin are released
Schematic representation of TLR4 signaling (adapted from  and )
Regulation of ER-stress by p38 and tumor dormancy
Activated receptor tyrosine kinases (RTKs) signal through scaffolding adaptors (e.g.
When ligands such as growth factors or insulin bind their receptor tyrosine kinases (RTKs) the RTKs dimerize and activate their kinase activity, resulting in phosphorylation of tyrosine sites on adaptor proteins such as the insulin receptor substrate (IRS) family
We propose that Ras/PI3K/PTEN/F-actin components form a feedback loop that is activated autonomously and without extracellular stimuli
IFN action is mediated via three receptor complexes: heterodimers between IFNAR1 and IFNAR2 bind type I IFNs; IL10R2 associates with IFNLR1 to bind the three IFNŒª; and a tetramer consisting of two IFNGR2 receptor chains with two IFNG1 receptor chains binds dimers of the type II IFNγ
Graphic illustrating the roles of 8 genes implicated in the present study in lithium-sensitive signaling pathways
Proposed biosynthetic pathway for MDP chromophore: (A) aminosugar; (B) β-hydroxy acid; (C) 3,6-dimethylsalicylyl-CoA; and (D) enediyne core and convergent biosynthesis of four components to yield MDP chromophore
(A) When Wnt signaling is “turned off”, cytoplasmic β-catenin is degrade... (B) When Wnt signaling is “turned on”, Wnt protein binds its receptor Fr...
. Schematic Representation of Hematopoietic Development during ES Cell Differentiation Summarizing the Role of the Different Signaling Pathways Identified in This Study.
PPAR-γ in Type 1/Type 2 T (NK) cell differentiation
IL-6 signaling and therapeutic targets in CCA
Model of Foxo3 regulation by PI3K-Akt signaling pathway within oocytes in the control of primordial follicle activation
Extrinsic and intrinsic pathways of hepatocyte apoptosis
The central role of hepatocyte apoptosis in liver injury
(A). A schematic, simplified apoptosis pathway. XIAP inhibits apoptosis... (B). Design of bivalent Smac mimetics to target both the BIR2 and BIR3 d...
MSn fragmentation scheme defining the major fragmentation Pathways I and II, of Francisella lipid A species and isobaric lipid A species featuring heterogeneous acyl chain distribution
Display of differentially expressed genes in the uterine cervix after term spontaneous labor mapped on the PLAU signaling pathway
PGE2 formation and its signal transduction pathways
Ischemia induces cell death by several distinct pathways, and Hsp70 reduces all of these
A molecular pathway triggered by RAR-β2 for the suppression of human carcinogenesis
Phospholipase A2 (PLA2) catalyzes phosphatidylcholine into AA in response to agonist stimulation of a G-protein–coupled cell surface receptor
Mechanisms that may result in perturbed neuronal Ca2+ homeostasis in Alzheimer’s disease
Flow-mediated dilation involves the activation of extracellular structures, which stimulate the F-actin network and membrane-anchored complexes
A diagramatics representation of the estrogen signal transduction pathway
These data suggest that arsenicals activate MAPK signaling both through ROS, as well as by direct association ()
After EGF binds to its receptor, conformational changes induce the activity of the Tyrosine Kinase domain (TK)
When TRAIL binds to Death Receptor 4 (DR4) or Death Receptor 5 (DR5), the Death Inducing Signal Complex is formed
A representative schematic for the pathways is shown
During stimuli such as oxidative stress, FoxO can be linked to a number of pathways that directly modulate FoxO activity, such as protein kinase B (Akt), the IŒ∫B kinase (IKK) pathway, and NF-Œ∫B, or that require FoxO to ultimately determine several cellular processes such as cell cycle regulation, apoptosis, immune system modulation, and malignancy
The five major cell signaling pathways are illustrated and described in the text
Osteoblasts, the niche cells in this model, express the parathyroid (PTH) and parathyroid-related peptide receptor (PTH1R)
Zymosan activates TLR2 and perhaps another unidentified subclass of the TLR receptors
Fibrillar Aβ activates the classical (and alternative) pathway of complement, resulting in C3b/iC3b deposition on plaques, glial recruitment and generation of neurotoxic molecules, and potential lysis by the Membrane attack complex (MAC/C5b-9) of complement
Iron–sulfur (Fe-S) cluster biogenesis in eukaryotes
The two pathways via which binding of cardiotonic steroids to the Na+/K+-ATPase exerts genomic and non-genomic effects
Oxysterols activate two distinct signaling pathways: 1) the hedgehog signaling pathway, and 2) a Dkk-1-inhibitable & β-catenin/TCF/Lef independent pathway
Schematic of therapeutic targets of the AR pathway
Most prominently involved biological pathways in OSCC
RLR signaling pathway and its negative regulatory molecules
The two subunits of the mature NOTCH1 receptor are generated by cleavage by a furin protease in the trans-Golgi network soon after translation of NOTCH1 precursor protein
. Schematic of cellular response to injury and trinucleotides.
Classification and regression tree analysis of genetic polymorphisms in cell cycle pathways and smoking status with OPL risk
A proposed model for transcriptional regulatory mechanism of canonical Wnt/β-catenin/Tcf4 signaling pathway by Smad2 and Smad4
Metabolism of sulforaphane involving (A) hydrolysis of glucosinolate to its isothiocyanate via myrosinase enzyme activity and (B) metabolism of SFN via the mercapturic acid pathway
Proteins from infected microglia co-cultured with astrocytes, separated by DIGE and identified by LC/MS/MS () were analyzed by dynamic pathway modeling
Hypothetical model for AVP concentration-dependent transitions between Ca2+ entry and Ca2+ release
Activation of the mammalian target of rapamycin (mTOR) pathway can result from numerous glioma-associated genetic changes
Information flow through the JNK network
Arachidonic acid, released from membrane phospholipids by cytosolic phospholipase A2 (cPLA2), can be metabolized by the 5-lipoxygenase (5-LO) pathway to make leukotrienes (LT) or by the cyclooxygenase pathway (COX) to make prostaglandins (PG)
Apoptotic cells or mAb217 up-regulate TGF-β mRNA expression through p38 MAPK, ERK and JNK, and enhance protein translation through and enhance protein translation through RhoA/PI3K/Akt/mTOR/eIF4E signaling pathway
The PI3K/PTEN/Akt/mTOR and Raf/MEK/ERK PI3K/PTEN/Akt/mTOR and pathways are regulated by upstream growth factor and mitogen receptors as well as Ras and various kinases
Amplification of HER2 is observed in 25 to 30pct of breast cancer patients which can result in activation of both the PI3K/PTEN/Akt/mTOR and Raf/MEK/ERK cascades
Highly simplified diagram of signaling pathways involving β-catenin that may be relevant for RPE cell morphogenesis and susceptibility to age-related oxidative stress
Possible scenarios for coupling between Stim1 and Orai1 in SOC activation
PCA (10mg/kg) administration induced robust Fos-IR throughout the adult lesioned (3A-1) and intact (3A-2) striatum as well as in the neonatal lesioned (3B-1) and intact (3B-2) striatum, demonstrating that PCA activates striatal neurons
DOI (5mg/kg) administration produced robust Fos-IR throughout the adult lesioned (5A-1) and intact (5A-2) striatum as well as in the neonatal lesioned (5B-1) and intact (5B-2) striatum, demonstrating that DOI activates striatal neurons
Animals pretreated with vehicle and then with DOI (5mg/kg) showed the characteristic Fos response in both the lesioned (6A-1) and intact (6A-2) striatum, as well as the characteristic pERK1/2 response (6C-1) in the neonatal lesioned striatum
This diagram summarizes the switch from dopamine and serotonin mediated transmission (top), to serotonin mediated transmission (bottom) in direct pathway striatal neurons following neonatal 6-OHDA lesions
PKCβII activates the Wnt/APC/β-catenin proliferative signaling pathway by inactivating GSK-3β and increasing the levels of β-catenin ()
A model of the involvement of TNFŒ±-mediated signaling pathways in insulin resistance
TGFβ pathway as affected by IGF2 administration based on Pathway-Express
PI3K pathway as affected by IGF2 administration based on Pathway-Express
Sulfur switches can exist as "Redox Sensors" and as "Redox Rheostats" in generic redox circuitry models
mTOR signals through two functionally distinct macromolecular complexes, mTORC1 (raptor complex) and mTORC2 (rictor complex), which are rapamycin-dependent and rapamycin-independent, respectively
Photic input from the retina induces the release of glutamate and PACAP from RHT terminals
Model based on studies of the activation of JNK pathway upon generation of H2O2 in rat alveolar macrophages () and in human bronchial epithelial cells (HBE1) exposed to HNE ()
Following stimulation with single stranded (ss) RNA, TLR7/8 recruit MyD88, IRAKs and TRAF6 to activate 2 distinct pathways
Wnt ligand interaction with the LRP receptor complex activates the pathway and β-catenin levels increase intracellularly
Schematic diagram illustrating two opposing signaling pathways activated by DFMO-mediated polyamine depletion in NB cells
Model of TNFR1 and LTβR ligation-induced signaling in vascular EC
The key event is an increase in plasma FFA concentration
Activation of NF-Œ∫B can occur by classical or alternative pathway
Possible scheme for ES cell differentiation and the role of specific factors in the formation of primitive ectoderm and primary germ layers
The example shown is insulin binding to the insulin receptor, which leads to the phosphorylation of insulin receptor substrates (IRS) that can bind, and thus activate, PI3K
The phosphatidylinositol 3′-kinase–Akt–mammalian target of rapamycin (PI3K–Akt–mTOR) pathway is shown
The many activating and inhibitory mechanisms that are used by DNA viruses to maintain mTOR complex 1 (mTORC1) activity and cap-dependent translation are summarized
In general, cytokine binding to a cognate receptor results in activation of the JAK/STAT pathway and induction of Socs gene transcription in a STAT-dependent manner
Dynamic DAT trafficking is a rheostat that fine-tunes DA signaling
Schematic representation of the three signaling pathways of apoptosis: The death receptor pathway through ligation of TNFR or Fas (extrinsic signaling), the mitochondrial pathway through Bcl-2 family members (intrinsic signaling), and the ER stress pathway
Bcl-2 (and Bcl-xL) inhibits apoptosis by blocking activation of Bax (and Bak) to prevent MOMP and subsequent release of cytochrome c and other apoptogenic proteins from the mitochondria
The autophagy regulator Atg 5 induces caspase activation by interacting with the adaptor protein FADD, a component of the extrinsic apoptosis pathway
(A) E2 interacts with ERŒ± locali zed at the neuronal (plasma) membrane and activates group 1 and group 2 metabotropic glutamate receptor (mGluR1a, mGluR2/3) signaling
The Hh-Gli pathway and the Gli code in tissue patterning and stem-cell lineages
Top-scoring gene networks, which are determined by ingenuity Pathways systems analysis of age and oxidative stress gene signatures in oestrogen receptor (ER)-positive breast cancers, commonly identify tumour necrosis factor (TNF) and transforming growth factor-β (TGFβ) pathway nodes
Nrf2-dependent genes identified by oligonucleotide microarray analysis are depicted in shaded squares
Working model of the Smac-mimetic IAP-inhibitors in radiosensitization
Both SIRT1 and AMPK are activated by CR, starvation, exercise, and RSV
An overview of the pathways involved in folate-dependent methionine transmethylation and transsulfuration
Human CG binds to the LHR and activates the Gs and Gq/11, families of G proteins leading to an increase in cAMP, inositol phosphates (InsP) and diacylgylcerol (DAG) as shown
Schematic diagram of a theoretical pancreatic endocrine tumor cell, smooth muscle cell (pericyte) or endothelial cell demonstrating the sites and mechanism of action of novel agents for the management of metastatic PETs
Components in the TNFR1 and LTβR pathways for NF-Œ∫B activation
Diagram showing the interactions of the cell signaling studied in sensitive and resistant lines
The canonical and noncanonical NF-Œ∫B signaling pathways
Schematic overview showing the membrane oestrogen receptor (mER) -mediated modulation of neurotransmitter regulated, G protein-coupled receptors in arcuate (POMC) neurones
PKCŒ± phosphorylates Bcl-2 at serine 70, preventing Bcl-2 from degradation
Upon binding IGF, the IGF-1R recruits scaffold proteins that direct the intracellular signaling down two major IGF-responsive pathways
The extrinsic apoptosis pathway is mediated by death receptors, resulting in sequential activation of initiator caspase 8 and executor caspases 3 and 7
Biological network of selected genes that were only induced more than twofold (P < 0.01) in the r1918-infected mouse lung compared with uninfected controls.
Nishino et al () raise two questions: 1) whether inhibition of GSK is required for protection in mice, and 2) whether inhibition of GSK is protective in mouse hearts
(A) Following TNF binding to the TNFR, the adap... (B) Binding of LPS or IL-1 results in receptor... (C) Activated IKK phosphorylates IŒ∫BŒ± or IŒ∫B...
Role of the ATM-p53 pathway in IR-induced apoptosis of developing CNS
Overview of Wnt/β-catenin signaling pathway in leukemia
Regulation pathways of Arc transcription in BDNF- and Ca2+-mediated signaling
Regulation of G1/S transition by growth factor (insulin and IGF-I) signaling in β-cells
FoxO proteins employ multiple signal transduction pathways that affect cell proliferation, survival and immune system function
Activation of DAF-2 potentiates the generation of PIP3 by AGE-1, which in turn activates PDK-1
(A) The FARP2/R-Ras/talin pathway. When plexins are inactive, the Rac GE... (B) The Fes/CRMP2 pathway. When stimulated by a class-3 semaphorin, A-pl...
The binding of the TNF trimer to TNFR1 causes trimerization of TNFR1, resulting in formation of the Complex I consisting of TNFR1, TRADD, TRAF2 and RIP
Schematic adapted from two recent reviews[,]
2.1 Regulation of the Actin Cytoskeleton; 2.2 MAPK Signaling Pathway.
UVB light stimulates the release of arachidonic acid from keratinocyte cell membranes and increases COX-2 and various prostaglandin synthases and prostaglandin receptors (indicated by the arrows pointing upward) that contribute to its biological effects in the skin
Each TLR recognizes a different microbial component
The leptin receptor shares several signaling cascades with other receptors found in the brain
Stepwise respecification of ETP and DN2 cells by GATA-3 overexpression
Myeloid diversion pathways for advanced pro-T cells by re-introduction of C/EBPŒ± or PU.1
After the induction of apoptosis, selective permeabilization of lysosomal membrane results in the release of mature CD into cytosol
The over-expressed pCD escapes normal targeting pathways and is secreted by the cancer cells
A VTA dopamine neuron is shown innervating a NAc medium spiny neuron
Kinetic Scheme for the 5-HT1AR and 5-HT2AR mediated MAP kinase activation pathway
Model of activation of Nrf2-mediated ARE pathway by phytochemicals
Role of IRS-1 in insulin and IGF-1 signaling
A. Schematic of structure of the HEF1/NEDD9/CasL protein.
Mechanisms of Smad3 in TGF-β–induced antiproliferative transcriptional responses
Mechanisms of Smad3 in TGF-β–mediated proapoptotic transcriptional responses
These pathways putatitvely influence the morphology of radial glia, as well as the ability of radial glia to provide a scaffold for migrating neurons and generate new neurons
Insulin and amino acid signaling pathway leading to the stimulation of translation initiation
Transcripts with an abundance of two-fold or greater in PACAP-treated (6 h) compared to vehicle-treated bovine chromaffin cells by two-color microarray analysis (187 transcripts; see ) were used as the input for analysis of potential networks using the signal transduction knowledge environment of Ingenuity (http://www.ingenuity.com).
A role for PPAR signaling in alternative (M2) macrophage activation
Retinoic acid (RA) is produced from vitamin A (retinol) via a two-step enzymatic pathway that oxidizes retinol to retinaldehyde and then retinaldehyde to RA
Posttranscriptional regulation of gene networks by GREs
We have previously shown that ICP10PK activates Ras by phosphorylation (inactivation) of the negative regulatory GTPase Ras-GAP (), as well as recruitment of the Grb2/Sos complex () and it, in turn, activates the Raf-1/MEK/ERK downstream pathway components (, ; )
Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are nuclear receptors able to function as ligand-activated transcription factors through binding to retinoic acid DNA response elements (RARE)
Working model of the signaling pathway components that are differentially regulated in C57BL/6 and CD-1 pup brain tissues and cultured NPCs under normoxic and hypoxic conditions
Tumor metastasis is a result of complex interplay of both positive (a) and negative (b) factors
Interleukin (IL)-6-signaling pathways with potential drug targets
Proposed signaling pathway underlying PMA-induced activation of the Tspo promoter
A model for the specific desensitization of GCB by S1P
A model of estradiol action on hypothalamic cells involved in the regulation of the LH surge
(A) Diagrams of 4-cell and 8-cell embryos and L1 larva, showing blastome... (B) Abbreviated C. elegans endomesoderm network (; ; ; ). Solid, lined a...
Model showing the activation of the JNK pathway upon challenge by UVB
The lipid kinase PI3K is activated in response to mitogenic signals and phosphorylates the phosphoinositides PI(4)P and PI(4,5)P2 at their D3 position, generating PI(3,4)P2 and PI(3,4,5)P3, respectively
The mTOR pathway is regulated by mitogen-responsive signaling pathways (shown in green), as well as by pathways that signal the availability of nutrients, such as amino acids (shown in yellow), and intracellular energy (shown in blue)
Because AMPK inhibits mTORC1 by direct and indirect mechanisms, drugs that activate AMPK could be effective in the treatment of cancer
Hypoxia and FFAs in obesity lead to activation of NF-kB pathway, which induces expression of inflammatory cytokines (TNF-a, IL-1, IL-6, et al) in adipose tissue
Enzymes controlling NAD metabolism in professional antigen presenting cells (PAPCs; microglia, macrophages, or dendritic cells) are shown with consideration of pharmacological administration of complementary NAD precursors or effectors of NAD utilizing enzymes (SIRT1 activators / PARP-1 inhibitors) towards rescue NAD deficiency arising from chronic inflammatory disease
(a–e) Shown are the PPP and glycerol synthesis pathway (GSP) (a), along with activity motifs identified in four different conditions (b–e)
Binding of TWEAK to Fn14 receptors leads to the activation of TAK1 and Akt through recruitment of TRAF-1, 2, 3, and/or 5 proteins
TLRs/NODs and key intracellular signaling cascades
Keap1 is a key regulator of the Nrf2 signaling pathway and serves as a molecular switch to turn on and off the Nrf2-mediated antioxidant response
Panel 1A: This figure demonstrates a highly abstracted schematic of the components and interactions of the BNG model
The PML regulon model is used to explain the effects of the PML protein and PML nuclear bodies on survival signaling as described in the text
During ANS development, transcription factors act in a network to induce other transcription factors
(A) In the absence of Shh, Ptch localizes to the primary cilium and, thr... (B) In the presence of Shh, Ptch is internalized, allowing Smo to traffi...
In Hh-dependent cancers such as BCC and medulloblastoma, the cilium may modulate the activity of signaling pathways in addition to Hh
Schematic diagram of cellular retinoid metabolism
Significant genes from EDGE analysis (see ) were used to visualize phenobarbital-induced temporal changes in the pathway (Ingenuity Pathways Analysis) for Car-mediated xenobiotic metabolism in mouse liver
Expression of genes contributing to the DNA Replication, Recombination, and Repair, Cell Cycle, Cell Death Network (left) was visualized using Ingenuity Pathways Analysis software at 7 days of phenobarbital and 28 days of WY-14,643 treatment
The schematic shows differentially expression of members of the Wnt pathway in castrate resistant prostate cancer and the impact on AR transcriptional activity
(A) Pathway maps generated using GenMapp depict... (B) Corresponding mRNA levels of glycolytic gen... (C) Increased glycolytic gene expression follow...
Activation of GPCRs activates phospholipase C and production of DAG and IP3
EGFR is activated by ligand binding and subsequent receptor heterodimerization or homodimerization which leads to receptor autophosphorylation
Activation of the AHR pathway results in the improper expression of R-Spondin1, which acts through LRP6 to activate Wnt/β-catenin signaling
LPA and S1P activate specific G-protein-coupled receptors (LPA1–4 and S1P1–5, respectively) and initiate Ras/ERK, PI3K/Akt, and Rho/ROCK signaling pathways in microvessel endothelial cells
PYK2 (protein tyrosine kinase 2); PXN (paxillin); FAK (focal adhesion kinase); SOS (son of sevenless); GRB2 (growth factor receptor-bound protein 2); GAB1 (GRB2-associated binding protein 1); RHO (Ras homolog gene family); RAC1 (ras-related C3 botulinum toxin substrate 1); CDC42 (cell division cycle 42); Pl3K (phosphoinositol 3 kinase)
Interleukin-31 acts through three signaling pathways: Jak/STAT pathway, PI3K/AKT pathway and MAPK pathway
Ligation of LPA to G protein-coupled LPA receptors results in IL-13RŒ±2 expression through activation of PLD and JNK/AP-1
Ligation of LPA to its G-protein-coupled receptors induces phosphorylation of EGF-R through PKCŒ¥, Lyn kinase, MMP, and pro-HB-EGF pathway
Cascade of events that follows a hypoxic-ischemic insult and over-stimulation of glutamate receptors in the brain
Sphingomyelinases cleave sphingomyelin (represented as small circles around the membrane) to ceramide in response to different extracellular insults
T cell differentiation proceeds along distinct pathways following antigen presentation by DCs
C. pneumoniae infection mediates foam cell formation through at least two signalling pathways: TLR2 and TLR4-dependent signaling through MyD88, and TLR4-TRIF-dependent signalling.
Primed ssDNA accumulates at stalled replication forks when a polymerase stalls
N-methyl-D-aspartate receptor (NMDAR) function can be positively regulated by Œ± calcium calmodulin kinase (Œ±CaMKII) phosphorylation and by the transient activation of cyclin-dependent kinase 5 (Cdk5) through the positive regulator p25
A) The endogenous odorant receptor signal transduction pathway in an olf... B) The heterologous odorant receptor signal transduction pathway in Hana...
Shown is a model where RGS4, RGS5, and RGS16 are cotranslationally degraded through serial Cys-2 modifications (see the main text)
Proposed pathways influencing adiposity in C
Drug-initiated microtubule disassembly mobilizes several signaling pathways that impact PAI-1 transcription
Schematic representation of interactions between injury and endogenous repair processes
TLR signaling and the role of epithelium in corneal innate defense
Proposed Src involvement in HCEC wound healing
TLRs such as TLR2, 4, and 5 at the cell surface of HCEC recognize PAMPs such as lipoproteins, LPS, and flagellin, respectively
It has been shown that ASCs mediate cardioprotection by producing and releasing soluble mediators with known cytoprotective properties
TGFβ/Smad superfamily signal strength is regulated and modulated at several different levels, both intrinsically and through cross-talk with other signaling pathways
Proposed model of TβR signaling pathway in normal human keratinocytes and squamous carcinoma cells
Angiotensinogen (AGT) produced by glial cells is transformed by renin to form Ang-I, which is then converted by ACE into Ang-II
Molecular scaffolds regulate the subcellular distribution of components of the MAPK pathway
Tumorigenesis in the adrenal cortex, like in other endocrine (i.e
Three possible mechanisms for constitutive activation of NIK have been considered: 1) NIK could be mutated such that it is constitutively active; 2) NIK could be activated by upstream activators; or 3) NIK could be activated through an autocrine loop
The Rho GTPase mechanochemical signaling apparatus links transmembrane and intracellular signaling-associated Rho GTPase with functional alterations in the actin cytoskeleton
Cardiac myocytes respond to altered haemodynamics by activating multiple intracellular signalling pathways that are implicated in the maintenance and regulation of cardiac myocyte fucntion
Antigen-induced aggregation of IgE-occupied FcεRI induces activation of the Src family tyrosine kinase, Lyn, whereas SCF-induced KIT dimerization induces activation of its intrinsic KIT kinase activation
A generalized schematic presentation of signaling pathways targeted by molecular therapies in malignant glioma
Simplified model for the involvement of cell cycle proteins in the regulation of survival and differentiation by neuronal chemokine receptors: SDF-1Œ± may affect expression of survival genes by regulating Rb and E2F-1 function
The transcription regulation of mitochondrial gene expression by CREB, ER, GR, and PPARγ2 have been reported
Schematic representation of growth factor interaction with growth factor receptors on the cell surface to initiate PI3K/Akt pathway responsible for cell cycle progression, survival, and proliferation
A. Transported substrates of P-glycoprotein (P-GP), also known as multidrug resistance gene 1 (MDR1), and as ATP binding casette B1 (ABCB1), multidrug resistance protein 1 (MRP1)/ABCC1, breast cancer resistance protein (BCRP)/ABCG2 and Ral binding protein 1 (RalBP1)/Ral interacting protein, 76 kDa (RLIP76).
PBT-1 induced genes in different pathways according to the KEGG and BIOCARTA pathway databases
PLA2 and PI3K/PTEN regulate chemotaxis in Dictyostelium
Signaling during the early (A, B) and late (C, D) phase of neuromuscular synapse formation
ALPS and CEDS illustrate signaling pathways for lymphocyte apoptosis and activation
Under normal levels of pO2 HIF-1Œ± is rapidly degraded via an ubiquitination pathway
The mitogen-activated protein kinase (MAPK) signaling pathway is physiologically activated by binding of growth factors to receptor tyrosine kinases (RTKs), such RET and NTRK, resulting in receptor dimerization and activation via autophosphorylation of tyrosine residues in the intracellular domain
A unifying model of Wnt signaling with regard to cardiomyogenesis
A, Highest scoring curated pathway regulated by GnRH in the absence of activin (P = 9.9 × 10−6).
A, Highest scoring curated pathway regulated by GnRH in the presence of activin (P = 1.5 × 10−6).
(A) Epithelial or astrocyte migrating into a wound area; (B) neuronal cell extending axon and dendrites; (C) Cytoskeletal organization and signaling proteins at the leading edge: The actin (G- & F-actin) cytoskeleton (red) provides a membrane protrusive force by actin polymerization at the leading edge
Tolerance to the downstream inflammatory effects of TLR4 activation
GST-MDA-7 causes PERK-dependent vacuolization and JNK pathway activation in transformed cells that leads to cell death
Various members of the TNF receptor super-family utilize the NF-Œ∫B signaling pathway to effect diverse physiological responses through NF-Œ∫B dependent gene expression program
Mechanism of action of toll-like receptors (TLRs)
Inhibition of apoptosis in Drosophila cells by DIAP1 occurs through binding to the initiator and effector caspases, Dronc and DrICE
Regulation of p53 and MDM2 and the outcomes of p53 activation
Biochemical effects of gene fusions cluster around tyrosine kinase (TK) signaling pathways, which alter the activity of intracellular proteins, and transcription factor (TF) activity, which control gene expression at the DNA level
Pathways analysis on the set of genes contained in the SNP component
Genes appearing in the second cluster of the rolipram-sensitive ANOVA analysis were connected using Ingenuity Pathway Analysis to cyclic AMP and the cAMP-regulated transcription factors CREM, CREB, and ATF-1
Both families of neurotrophic factors employ a two-receptor complex to produce specific growth factor effects
Schematic of a novel pathway for heme oxygenase/carbon monoxide-dependent cyclic GMP signaling based on the newly described sGC/cyclic GMP-modulating agents YC-1 and BAY 41-2272 as shown
[selected findings of recent studies with relevance to Tgf-β superfamily signaling in endocardial EMT have been summarized]
mTORC1 activation by nutrients and growth factors
ONE induces strong ERK activation at an early time point, which is subsequently followed by p53-mediated apoptosis
PML could regulate mTOR activity through nuclear Akt function, mTOR-Rheb interaction and PTEN localization [,,]
Activation of AMPK leads to the inhibition of cholesterol synthesis by the phopshorylation of HMG-CoA reductase
After an inciting event, inflammatory or angiogenic activity (MMP, VEGF) initiates microvascular growth and remodeling, which are stabilized through interplay of pathways including TIE-2/ANG and TGF-β or BMP-9 signaling through the ALK-1/ENG pathway
Cell cycle regulation pathway was modified from KEGG and a knowledge based pathways about NRf2-mediated oxidative stress response and IL6 and NFκB were built in GenMAPP program (www.gennmap.org) ().
Abl kinases are activated in response to TCR stimulation in a pathway that requires Lck kinase activity
The conversion of subendothelial macrophages into cholesterol-laden foam cells is believed to constitute the foundation of the atherosclerotic lesion
Schematic diagram of the VTA-NAc-VP reward pathway, illustrating the actions of psychostimulants (including cocaine, amphetamine, methamphetamine) on extracellular DA, endocannabinoids (eCBs), glutamate and GABA in both the NAc and VP, and the sites of action of 6 classes of mechanism-based pharmacological agents in development for the treatment of psychostimulant addiction, as reviewed in the present article
The killing of E. hitolytica trophozoites by macrophages is mainly mediated by nitric oxide, derived from L-arginine by nitric oxide synthase (NOS).
Involvement of p53 signaling after ROS generation
This cell signaling pathway is important for the cellular response to a variety of growth and differentiation factors
The roles of TLR signaling in glial cells, endothelial cells, leukocytes and neuronal cells during the pathogenesis of ischemic stroke
The NLR Nod2 recognizes bacterial PGN fragments such as MDP and activates NF-Œ∫B and MAPK signaling via the indicated proteins leading to the transcriptional upregulation of a variety of proinflammatory cytokines and antimicrobial peptides
Micorarray experiments were performed on lung material from six SARS coronavirus (SARS-CoV)-infected macaques []
Regulation mechanisms for Itch-mediated Th2 differentiation.TCR triggering plus CD28-mediated costimulation results in the activation of MEKK1-JNK signaling pathway, which induces the serine/threonine phosphorylation of Itch
Endogenous Abl kinases directly phosphorylate SHP-2 on Y580, which increases sustained ERK activation in response to PDGF (Figs
ErbB proteins are type I transmembrane receptor tyrosine kinases
In non-canonical forward signalling (bottom cell, right-hand pathway), the carboxy-terminal fragment (ErbB4-CTF) is cleaved by γ-secretase to produce ErbB4-intracellular domain (ErbB4-ICD), which can translocate to the nucleus to regulate gene expression
Occupation of the GPCR leads to activation of PI3-kinase, phosphorylation of phosphatidylinositol bisphosphate, and activation of the phosphatidylinositol-dependent kinases (PDKs) []
SAC localizes to the cytoplasm and nucleus when it is over-expressed in cells
Binding of TSLP to its receptor complex results in the phosphorylation of STAT-5 and STAT-3, although the involvement of a specific JAK has not been elucidated (A)
Testosterone, produced by the perinatal testes, regulates cell number in several sexually dimorphic areas
Induction of IFN-signaling pathways in HCV-infected uPA-SCID mice (A) and patients (B)
A schematic diagram of a memory CD4 T cell is shown with surface TCR and CD28
Activators and inhibitors of the various steps of the CO2-HCO3−-sAC-cAMP-PKA pathway are indicated
RNA polymerase III transcription is elevated during late G1, S, and G2 phases and becomes repressed during M and early G1 phases
During development, HGF-Met binding promotes receptor kinase activation and tyrosyl phosphorylation of junctional β-catenin, resulting in its dissociation from E-cadherin and cytoplasmic accumulation
The model is based on the current findings and our previously published studies (, ‚Äì)
Binding of VEGF and FGF to their receptors on ECs leads to activation of the MAP kinase signaling pathway, which culminates in the nucleus to stimulate the transcription of genes involved in angiogenesis
Carbon flow from [U-13C]-glucose through glycolysis, Krebs cycle, PPP, pyruvate carboxylation, malate/Asp shuttle, and synthesis of GSH and pyrimidine nucleotides
Briefly, the Phagocytosis Phase is characterized by the uptake of WGPs by gastrointestinal macrophages that are associated with M cells within the gut-associated lymphoid tissue (GALT) near the Peyer’s patches
A: Signaling pathways activated by IGF1 or AR growth factors used as sin... B: Survival pathway activated by the cooperation of IGF1 and AR growth f...
The VHL gene complex targets hypoxia-inducible factors (HIF) for ubiquitin-mediated degradation
Proposed mechanism of PAF-induced enterocyte apoptosis and its inhibition by PUFA
A schematic illustration of BER subpathways for damaged bases and DNA strand breaks
HuR and/or AUF1 differentially regulate mRNAs encoding cell cycle and Erk1/Erk2 Mapk signaling-related genes in MCT-1–transformed cells
Regulation of endothelial nitric oxide synthase (eNOS) by ROCKs
Mechanisms that have been implicated in the hypoxia-induced elevation of [Ca2+]i, and their potential signalling pathways
Unifying model of TGFβ signaling in breast epithelium
Proposed pathway for the interaction between ERŒ± and growth factor (GF) signaling pathways and regulation by estradiol (E2) and progesterone (P4)
Schematic representation of the steroidogenic cascade involving the steroid hydroxylating cytochromes P450 (P450) that catalyze cleavage and/or hydroxylation of sequential substrates from cholesterol through pregnenolone, androstane and estrane (synthesis)
Binding of S1P to the SIP1 receptor stimulates the Gi-dependent recruitment of PI3 kinase, Tiam1 and Rac1 to lipid rafts (CEM), which serves to activate Rac1 in a Gi-PI3K-Tiam1 dependent manner
BMPR1A signaling upregulates sclerostin expression, leading to an inhibition of canonical Wnt signaling and a decrease in bone mass by upregulating osteoclastogenesis through the RANKL-OPG pathway
4HPR mediates the neuronal differentiation of ARPE-19 cells by activating both c-Raf and MEK1/2, while the activation of its downstream targets such as SAPK/JNK and MAPK/ERK1/2 was regulated by MEK1/2
A proposed signaling pathway based on the results of the present study and that of Williams et al
After activation of membrane-bound microbial sensors such as Toll-like receptors (TLRs) and immunoreceptor tyrosine-based activation motif (ITAM)-containing non-TLRs, and the cytoplasmic sensor NOD2 (CARD15), signaling pathways converge on CARD9
Different forms of regulation of ion channels relevant to Ca2+signaling
A prime signaling cascade that mediates changes in [Ca2+]cyt (cytosolic) initiates with the activation of plasma membrane (PM) receptors (ex-GPCR, G-protein coupled receptor)
Role of BPI in the interaction of GNB and OM blebs with neutrophil granulocytes and monocytes (A)
Comparison of VPC and HCG patterning networks in C
Glucan synthase (GS), comprised of catalytic subunit Fks1 (or Fks2) and its activator Rho1, is responsible for synthesis of the principal cell wall component β-1,3-glucan
A “triple-switch” (transcription of PCK1, acetylation of Pck1p and allosteric modification of PC) in the gluconeogenesis pathway controls prompt adaptation of a metabolic flux to energy status in yeast (A) and humans (B)
The Raf/MEK/ERK pathway is regulated by Ras as well as various kinases, which serve to phosphorylate S/T and Y residues on Raf
Many other non MEK1/ERK mediated functions of Raf-1 have been postulated
The PI3K/Akt pathway is activated either by the p85 PI3K regulatory subunit binding to an activated tyrosine residue on the activated growth factor receptor or via interaction with Ras
Some of the potential downstream molecules activated by the Raf/MEK/ERK, PI3K/Akt and p53 and their effects on the induction of apoptosis are illustrated
This figure summarizes some of the complex interactions between p53 and the Raf/MEK/ERK and PI3K/Akt pathways
Potential sites of action of small molecular weight inhibitors are indicated
Sites of mutation which can result in activation of the Raf>MEK>ERK pathway
Effects of Raf>MEK>ERK and PI3K>Akt pathways on caspase 9 phosphorylation and the induction of drug resistance
These oscillating components were discovered by performing a KEGG Pathway Analysis using Genesifter software of the two pre-selected clusters comprising early and late oscillators (see )
Tumor cells contain multiple signal transduction pathways, some of which mediate cell survival, such as the PI3K-AKT and RAF-MEK-ERK1/2 pathways
Kinase inhibitors that modulate the cell cycle have frequently been combined with toxic drugs and/or radiation which cause DNA damage
The cellular events during autophagy follow distinct stages: vesicle nucleation (formation of the isolation membrane/phagophore), vesicle elongation and completion (growth and closure), fusion of the double-membraned autophagosome with the lysosome to form an autolysosome, and lysis of the autophagosome inner membrane and breakdown of its contents inside the autolysosome
The angiotensin receptor (AT1R) is coupled to the GTP-binding protein Gq
Schematic of proposed signaling pathways by which the Tec kinases regulate JNK activation, actin polymerization, and cytokine expression in LPS-stimulated neutrophils
Radiation-induced double strand breaks or gemcitabine-induced replication stress trigger the activation of ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) kinases, respectively ()
The great versatility of integrin receptors relies on their ability to form signaling complexes with many distinct signaling effectors
Activation of the multimeric IKK mediates the phosphorylation of IŒ∫B
Schematic pathway of signaling in Plasmodium
Activation of the AhR pathway alters cellular adhesion in a variety of model systems
(1) AhR pathway activation alters expression of both the uPA protease and PAI-1/2
Depicted are some of the processes known to take place between the AhR pathway; NFŒ∫B, Estrogen Receptor (ER), Retinoic Acid Receptor (RAR) and Transforming Growth Factor β (TGFβ) pathways
The inter-relationships of genes associated with apoptosis differentially expressed in the lacrimal glands of C57BL/6.NOD-Aec1Aec2 mice
Schematic showing inter-relationships of clustered genes associated with fatty acid, lipid and lipoprotein homeostasis based on differentially-expressed genes identified in lacrimal glands of C57BL/6.NOD-Aec1Aec2 mice
LPS activation of the mitogen activated protein kinases (MAPKs) induces the expression of tissue factor (TF) as well as the proinflammatory cytokine TNFŒ±
Increased basal HO-1 may confer cytoprotection against I/R injury by increasing Akt activity directly via phosphorylation of p85 and/or Akt by BVR and/or HO-1 itself
Load-driven signaling pathways predicted with ankle loading at 1 h after the last loading
The interactions of TAB1 and CD2AP with the TGF-β3/TGF-β-receptor complex can activate both the p38 or the ERK signaling pathways, which, in turn, causes the disruption of both BTB and AJs (right panel)
Models to explain HDAC-mediated regulation of MHC gene expression during hypertrophy
Φερριτιν βινδσ το υνκνοων ρεχεπτορ εξπρεσσεδ βψ αχτιϖατεδ ρατ HΣX ανδ ρτιμ υλατεσ α σιγναλλινγ χασχαδε τηατ ρεσυλτσ ιν τηε αχτιϖατιον οϕ NΦκB and subsequently enhances the expression of a number of NFκB-responsive genes including, IL-1β, IκBα, ICAM1, RANTES and iNOS
Interleukin-13 (IL-13) promotes collagen production by three distinct but possibly overlapping mechanisms
Synthesis of modified mannosamines and sialic acids
Autophagy proceeds constitutively at a low basal rate in most cells, and can be induced to high levels in response to starvation, loss of growth factor signaling, and other stressors
Proposed signaling pathway of the extracellular nucleotide-induced phosphorylation of eNOS in EC
Dicer-like proteins (DCLs) are represented in association with known and unknown cognate double-stranded (ds)RNA-binding proteins (DRBs)
Functional annotation of 115 C/EBPβ target genes presented in pie chart format shows that 74pct of target genes are dedicated to signaling, metabolism, and transport, with the remaining 26pct having roles in transcription, synaptic transmission, differentiation and proliferation
P. gingivalis is predominantly recognized by the TLR2/1 heterodimer [].
Drug-induced signaling events are depicted for cocaine/amphetamine, ethanol, and an inhalant, benzyl alcohol
Diagrammatic representation of hormone therapy-induced changes in gene expression in the dorsal raphe block
(A) Ligand activation of PPARβ/Œ¥ potentiates colon cancer. In this mode... (B) Ligand activation of PPARβ/Œ¥ attenuates colon cancer. In this model...
Major signaling pathways of cranial suture fusion
PRC compounds may selectively target cancer cells with high NQO1 enzymatic activity by oxidative-stress dependent induction of the mitochondrial pathway of apoptosis
PKCŒπ resides in several major signaling pathways implicated in human cancer
The classical pathway (solid gray arrow) involves the conversion of C21 precursors (pregnenolone and progesterone) to the C19 adrenal androgens DHEA and androstenedione (AED) by the hydroxylase and lyase activity of CYP17A1
Activation of EP4 receptor by PGE2 leads to phosphorylation of ERK via EGFR and its downstream MEK pathway
Direct and indirect interactions are shown in solid and dashed lines, respectively
ER stress leads to several redundant pathways for caspase activation that involve mitochondrial- dependent and independent pathways
Schematic representation of molecular changes from acute to chronic amphetamine exposures in ventral tegmental area (VTA) dopaminergic (DA) neurons
Regulation of L-type Ca2+ channel (LTCC) phosphorylation by psychostimulants
Schematic representation of molecular changes from acute psychostimulant exposure to persistent molecular changes in the nucleus accumbens (NAc) and dorsal striatum
Regulation of glycolysis, glutaminolysis and de novo nucleotide biosynthesis in tumor cells
(A) In normal cells, Top1-DNA covalent complexes can be repaired by redu... (B) Cancer cells might be more dependent on the Tdp1 pathway as a result...
Model of the role of MAPK cascades in cardiomyocyte hypertrophy
Notch signaling is initiated through binding of Notch ligands expressed an adjacent cell, followed by enzymatic cleavage and release of intercellular of Notch (ICN)
Wnt/β-catenin signaling in preadipocytes is initiated by expression of Wnt10b, Wnt10a, and Wnt6
Using TLR4, which can signal through both the MyD88 and TRIF pathways, as an example, this figure depicts how the shift from a proinflammatory to an anti-inflammatory response may be achieved to provide neuroprotection
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an antagonist of class I phosphatidylinositol 3—kinase (PI3K) signaling
The phosphatidylinositol 3—kinase (PI3K) signaling pathway
Mechanistic model of enhanced activation induced by the E545K mutation in p110Œ±
Feedback inhibition of the phosphatidylinositol 3—kinase (PI3K) pathway
Independent of its source (endogenous/exogenous), 17β-estradiol protects the hippocampus against cerebral ischemia via activation of CREB pathway
a | The canonical conjugation pathway for ubiquitin (Ub)
With a few exceptions expression of CD137 is activation dependent
The pathways represent data obtained from both forward and reverse genetic studies
(A) The IL-1 signaling loop is initiated by microbial stimulation of TLR... (B) ultimately causes chronic inflammation and autoimmunity in Ptpn6spin...
(A) Crz1 enters the nucleus in sho... (B) NFATc proteins are similar to... (C) Feedback loops in the calcineu... (D) NFAT target genes are activate...
MMP-9 expression is induced by proinflammatory stimuli (see )
Schematic representation of intracellular signaling resulting from activation of nAChRs, glutamate ionotropic receptors, and GABAA receptors
Major regulatory steps in the process of DNA damage response (DDR)
Schematic representation of ICP10PK-mediated neuroprotection from MPP+-induced PCD
Metabolic targeting strategies against malignant tumors that rely on HK-2 facilitated glycolytic flux
Recognition of poorly immunogenic tumor via endogenous and exogenous pathways
One possible pathway which regulates cell proliferation in response to strain on collagen
One possible pathway which regulates cell migration in response to strain on fibronectin
Effect of small DNA viruses on the ARF-p53 pathway
Gene regulatory networks in kidney development
Schematic representation of the concept of angiotensin II-growth factor cross-talk in ureteric bud morphogenesis
PGE2 stimulates the secretion of BDNF from both microglial and astrocyte human cell lines through the activation of the EP2 receptor and the cyclic AMP pathway
Pancreatic ductal adenocarcinoma (PDAC) is thought to arise from preinvasive PanIN lesions (top) that have sustained mutational activation of the Kras pathway
Paracrine and autocrine mechanisms of Akt-mediated tumor-stromal interactions
Components of the central activation cascade proceeding from ligand-bound EGFR through Raf to the nucleus are indicated in green or yellow boxes, connected by red arrows
The program STRING (‘Search Tool for the Retrieval of Interacting Genes/Proteins’, http://string.embl.de/) collects known physical interactions from the following databases: BIND, DIP, MINT, BioGRID, and HPRD.
A proposed signaling pathway of mmLDL-induced, TLR4/Syk-dependent ROS generation and proinflammatory cytokine expression
The p16 pathway blocks the CDK4-CDK6-cyclin-D complex which increases the phosphorylation state of RB, causing it to release the transcription factor E2F
Viral infection of cells initiates the homo-dimerization and subsequent phosphorylation and activation of interferon-induced, double-stranded RNA-activated protein kinase (PKR)
The Hippo pathway, a vital growth regulator of cell proliferation and apoptosis was initially identified by mosaic screens in Drosophila melanogaster (,)
(A) It has been proposed in L5 of visual cortex () that postsynaptic act... (B) Schematic for a possible postsynaptic coincidence detector for CB1-m...
Proposed pathway involved in the regulation of the osteoblast F-actin cytoskeleton, based upon previous literature and the current experimental results
BCL6 is expressed when B-cells enter the germinal center reaction
Exposure to cigarette smoke in susceptible individuals leads to an abnormal inflammation which appears to be self-perpetuating and is perhaps linked to infection
A schema for the signaling pathway regulated by NHERF
Three Gli proteins transduce the hedgehog signal
Viral ssRNA with 5′-triphosphate group and dsRNA are detected by the cytoplasmic pathogen recognition receptors, RIG-I and MDA5, respectively
The loading of 9-1-1 at RPA-coated gaps, generated during NER of DNA damage, activates Mec1
(A) A lag between checkpoint activation and CDK... (B) Phosphorylation of substrates involved in H... (C) Subpathways of CDK activation allow repair...
Regulation of IFN response genes by TLR3 signaling
The entrance of erythrocytes into tissue regions with a high oxygen demand [decreased oxygen tension (PO2)] results in diffusion of oxygen to the tissue and a decrease in the oxygen saturation (SO2) of the hemoglobin within erythrocytes in the microcirculation
Intracellular signaling consequences of calpain-mediated substrate cleavage
The retromer sorting pathway is made up of a coat complex that binds and transports transmembrane receptors between the endosome and the trans-Golgi network (TGN)
The C. elegans insulin–IGF-1 (insulin-like growth factor 1) like signal-transduction pathway is shown on the left, and human homologues of the proteins that are involved are shown on the right.
Proposed coloboma mechanism in Lrp6-null eyes and a possible signaling network during early eye development
Canonical Wnt signaling is initiated when Wnts bind to their cognate receptor complex of the transmembrane proteins Frizzled and Lrp
Multiple previously established signaling cascades in activated mast cells with quantitative proteomic data from MCP5 cells represented as heatmap bars beside individual proteins
Model for EGFR-dependent MAPK activation
Signaling via the JAK-STAT pathway by IFN-β (IFNAR2, JAK1, TYK2, PRKCA and PIAS1) [,,] causes upregulation (GBP1, PRKR, PNPT1, IL10) [,,,,] or downregulation (DUSP1 and LEP) [,,] of various genes
Ag triggering of the BCR initiates activation of PTKs Syk and Lyn
Schematic diagram depicting our findings on the post-transcriptional regulation of CXCR4 in MCF7-HER2 cells as a result of estrogen and HER2 cross-talk and the involvement of activated PI3K and MAPK pathways and TSC2 (tuberin)
Activation of receptor tyrosine kinases (RTKs) or G protein-coupled receptors (GPCRs) by growth factors or mitogens leads to the recruitment of an adaptor protein Grb2 (growth factor receptor bound protein) and the guanine nucleotide exchange factor (SOS)
Map of protein interactivity (binding, regulation, modification) between genes revealed to be significantly associated with bladder cancer in urothelial cell samples
Schematic diagram of the Wnt signaling network
The classical and alternative NF-Œ∫B signaling pathways are represented downstream of CD40 and BAFF-R
The immunological synapse or the interface between an antigen presenting cell and a T-cell
The ES-EB system has made possible the identification of multipotent progenitors for both hemato-vascular and cardio-vascular derivatives
A scheme showing the role of different signaling pathways in mediating the effect of high K intake on ROMK and BK channels in the CCD
A scheme showing the role of different signaling pathways in mediating the effect of low K intake on ROMK and BK channels in the CCD
Nm23-H1suppression of tumor metastasis may depend on at least three pathways
Proposed model of increase PTHrP expression in breast cancer cells
Activation of inflammatory pathway mediated through NF-Œ∫B by life-style related factors such as tobacco, stress, dietary agents, obesity, alcohol, infectious agents, irradiation and environmental stimuli that account for as much as 95pct of all cancers
Following breach of the epithelial barrier of the airways by environmental allergens, particularly in genetically susceptible hosts, APC process the allergen and upon presentation to T cells initiate an immune response
Overview of ligand and receptor endocytosis in the Notch signaling pathway
Ligand binding to inactive monomeric Her receptors is followed by dimer formation and kinase activation
Outline of the major cell surface receptor-mediated signaling pathways important in the differentiation, survival, and function of melanocytes
a | In the absence of insulin binding, FoxO is a transcriptional activator of multiple insulin-responsive (IR) genes.b | Engagement of the phosphatidylinositol 3-kinase (PI3K) pathway in response to insulin or other factors leads to the activation of Akt and to the phosphorylation (P) of FoxO proteins on crucial serine and threonine residues (Thr24, Ser256 and Ser319 in FOXO1)–.
A. A network connecting genetic and transcriptional data of STE5 deletion strain via paths of length ‚â§ 3 edges finds 193 nodes and 778 edges.B.
Regulation of STAT3 signal transduction pathway
Targeting the ASK1/MKK4/JNK pathway upstream of mitochondrial prodeath signaling
A generalized model for signaling through the NF-Œ∫B pathway
Swi6 promotes the stable association of nascent heterochromatic transcripts to sites of RNA synthesis by its ability to bind to H3K9me and RNA
Mechanisms of carcinogenesis of Bcr-Abl in CML
Mechanisms of VEGF/VEGFR-mediated protection of cardiomyocytes from pressure stress and ischemia, and potential interactions of sunitinib and sorafenib
Binding of TNFŒ± to its receptor induces the recruitment of signaling proteins, including the adaptor TRADD, ubiquitin ligases TRAF2, TRAF5, cIAP1 and cIAP2, and protein kinase RIP1
Contribution of Rho to canonical Wnt3A signaling
Binding of TNF-Œ± (TNFSF1A) to TNF-R1 (TNFRSF1) at the cell surface results in receptor oligomerization and recruitment of signaling intermediates TRADD, TRAF2, TRAF5, and RIPK1, leading to the activation of the IŒ∫B kinase (IKK) complex
The diagram shows the cell signaling pathways, which were involved in postconditioning
In resting cells, the majority of NF-Œ∫B is bound to I-Œ∫B inhibitory protein, often IŒ∫BŒ∫, which masks the nuclear localisation sequence (NLS) and holds the complex in the cytoplasm
A simplified model of the leptin signaling pathway
Dopamine controls many brain functions, including roles in behavior and cognition, motor activity, motivation, and reward
The commonly occurring guanine nucleotide biosynthetic and salvage reactions are shown, as is the adenine nucleotide biosynthetic pathway
At the left side of the panel, P. gingivalis W83 (injected in the bottom of mandibular anterior vestibule) stimulate TLR2 expressed by hitherto uncharacterized resident sentinel cells (e.g., gingival epithelial cells, macrophages, mast cells).
Multiple isoforms catalyze each step in the glycerol-3-phosphate pathway of TAG synthesis
Note that these are proposed models and it is possible, even likely, that the mechanism(s) by which these genes confer risk for SLE involve not only the pathways presented, but also other pathways.a | Phagocytosis.
Abbreviations: GST, glutathione S-transferase; γ-TP, γ-glutamyltranspeptidase; CG, cysteinylglycinase; NAT, N-acetyltransferase
Proposed model showing the role of ECM proteoglycans bgn and fmod in controlling the fate of tendon stem/progenitor cells (TSPC)
vMIA is expressed early during HCMV infection, protecting host cells from the intrinsic apoptosis pathway, presumably as a mechanism to aid viral replication
Schematic showing the pathway for synthesis and mode of action of prostacyclin (PGI2)
Upon binding to its dimeric receptor (IFNAR1 & IFNAR2), type I IFN promotes the apposition of two receptor associated JAKs (Jak1 & Tyk2), directing transphosphorylation and activation
TLR4 binds to LPS-MD2 complexes and engages MyD88- TIRAP adaptors at the cell surface leading to activation of early MAP kinase pathway
The broad range tyrosine kinase inhibitor AG18 blocks the potentiation of AR transcription by MAA
Metabolic cooperativity between oocytes and cumulus cells, and the role of oocyte-derived paracrine factors in promoting metabolism in cumulus cells
Key signaling pathways between amino acids, inflammatory cytokines, and tumor-specific factors gr1Amino acids stimulate muscle protein synthesis through the mTOR pathway
Schematic representation of a simplified cerebral ischemia induced cascade on synaptic dysfunction
Simplified scheme depicting the basic signaling pathways defined in ischemic preconditioning in mammals
The Ras/mitogen-activated protein kinase (MAPK) signaling pathway and associated developmental syndromes (indicated by dashed lines)
mTORC1 functions to integrates various upstream signaling pathways to regulate protein synthesis and cell growth
The Hh receptor Ptch is a transmembrane protein that inhibits the activity of Smo in the absence of Hh
Mechanisms underlying the pleiotropic effects of statins in stroke
Key components of the proposed PACAP-mediated signaling path as described in the text are shown
Improved readability and performance with multi-scale information integrated in pathway visualization using metagraph
Air pollution is a complex toxin causing diverse CNS pathology through several interrelated mechanisms that may lead to CNS disease
Based on present models for Ca2+-dependent regulation of transcription factors such as Nuclear Factor of Activated T-cells (NFAT) and Nuclear Factor kb (NF-Œ∫B), membrane potential modulation and direct Ca2+ entry through non-SOCE pathways are predicted to have the capacity to significantly alter B-cell-fate choice.A: Strong B-cell receptor (BCR) activation fully activates both NF-Œ∫B (through inhibitor of kb (IŒ∫B) degradation) and NFAT (through calcineurin phosphatase activation) pathways.B: Modulation of membrane potential attenuates late Ca2+ entry, selectively influencing NFAT activation.C: A weak but sustained BCR activation signal activates only the NFAT pathway.D: Late activation of a direct Ca2+ entry pathway restores NF-Œ∫B pathway activation despite a weak BCR activation signal.
Upon the stimulation by cognate ligands, all TLRs, except for TLR3, recruit MyD88, IRAKs and TRAF6 to activate TLR signaling
This proposed pathway is simultaneously initiated and performed within nuclei and mitochondria
Schematic representation of the role of adiponectin in blood pressure lowering
Overview of β-catenin signaling and its regulation
A. Under normal conditions in the developing brain, CGNPs are exposed to Shh and IGF.
A. TMPD stimulates IFNα and IFNß production by immature (Ly6Chi) monocytes.
Injury-induced changes in the nociceptive pathway
Pathway model for studying the influence of drug-binding kinetics on EGF signaling in non-small cell lung cancer
When induced to express IDO, pDCs may activate Tregs to create immune privilege, and block inflammatory signals that would otherwise stimulate effector T-cell responses
Negative- (closed arrow –•) and positive- (open arrow →) feedback loops involved in p53 signaling are highlighted and the manner in which they intertwine to synchronize regulation of the cell cycle with the regulation of protein synthesis
MTDH/AEG-1 promotes tumor progression through the integration of multiple signaling pathways
Ion channels have two key functional properties: ion selectivity - the ability to discriminate between the various common ions found in the cell
Death receptor 5 is a member of the TNF-receptor superfamily
After leptin binds to the long isoform of the leptin receptor (OB-Rb), Jak2 is activated at the box1 motif, resulting in the autophosphorylation of tyrosine residues and phosphorylation of tyrosines that provide docking sites for signalling proteins containing src homology 2 (SH2) domains
Panel A: During normal B-cell maturation, activated B-cells form germinal c... B: Translocations or point mutations of the BCL6 locus can cause it t...
Enzymatic pathways of the biosynthesis and degradation of the two main endocannabinoids, anandamide and 2-arachidonoylglycerol
(A) Protein interaction graph of the APC (center) axis. Nodes (n = (B) Map of the canonical WNT-signaling pathway, including APC (left, cen...
A hypothetical diagram of possible sites of action of non-opioids in the regulatory pathway of IL-6
A hypothetical diagram of possible sites of action of non-opioids in the regulatory pathway of MMPs
Antigens induce allergic responses via crosslinking of IgE-bound FcŒµRI receptors on the surface of mast cells, triggering elaborate signaling cascades that result in degranulation and immediate release of a plethora of inflammatory mediators
Activation of receptor tyrosine kinases (RTKs) recruits PI3K directly or indirectly via RAS to the plasma membrane, where it phosphorylates phosphosphatidylinositol-4,5-bisphosphate (PIP2) to generate the phosphatidylinositol-3,4,5-trisphosphate (PIP3)
Coverage of the insulin receptor signaling pathway
Diagrammatic representation of intracellular pathways of receptor-mediated endocytosis and trafficking: The ligand binding to specific cell surface receptor leads to a selective recruitment of ligand-receptor complexes into clathrin-coated pits
The role of FoxO factors in endothelial cells
The role of Akt-FoxO pathway in regulation of heart size
The differentially expressed gene list (53 entities) () was imported into the Pathway Studio program
(A) Canonical G protein signaling in the mammalian olfactory system (ACIII, adenylate cyclase III; CNGC, cyclic nucleotide-gated channel)
Scheme for up-regulation of the PAI-1 gene by EGF in glioblastoma
pDC utilize a variety of cell-surface receptors to endocytose viruses into endosomes where the viral nucleic acid is uncoated
The various steps in the MHC class II processing and presentation pathway that are known or postulated to be influenced by M. tuberculosis infection are illustrated.
Integration of ITAM and cytokine Jak–STAT signaling
Hypothetical schematic of a DAergic synapse
Our data indicate that it does so through signaling via Rac1, SSH proteins, 14-3-3 proteins, cofilin, and the actin cytoskeleton
LPS signal transduction via the MyD88-dependent pathway
LPS signal transduction via the MyD88-independent pathway
(A). A simplified phylogenetic tree of the POZ... (B). Examples of lineage-specific gene expansio... (C). The ubiquitin and kinase pathways are show...
Model for transcriptional regulation of human CYP17
Schematic illustration of CIE and CDE pathways showing lipid content and regulatory molecules
Adiponectin-mediated regulation of inflammatory responses in different cell types
PTHrP increases cell surface levels of integrin Œ±6β4, which signals synergistically with growth factor receptors to activate the PI3-K/Akt pathway
The overall rate at which cellular damage accumulates is regulated by multiple pathways (yellow components) and transcription factors (red) that adjust mechanisms for maintenance and repair
Insertion of the sublytic C5b-9 into the cell membrane leads to G-protein activation, followed by the activation of PI3K and Akt
LKB1 in complex with its two regulatory subunits STRAD and Mo25 directly phosphorylates and activates a family of 14 AMPK-related kinases
A number of inherited hamartoma and cancer predispotion syndromes all share in common hyperactivation of mTORC1 or HIF-1Œ±
The Par complex, composed of an atypical PKC family member, the Par-3 scaffold, the cdc42-binding Par-6, and cdc42 phosphorylates a number of downstream polarity proteins, including LKB1, the MARK family, and Lethal giant larvae (LGL)
Schematic representation of Trk receptor tyrosine kinases and major signal transduction pathways
IL-1β, PGF2α and PGE2 activate CREB-regulated COX2 and MUC5AC gene expression through PKA or PKC mediated MAPK/RSK pathway
The potential mechanisms of estrogen-mediated signaling through estrogen receptor (ESR) and G protein-coupled receptor 30 (GPR30)
Two major oncogenic pathways, the GTPase Ras/Raf/ERK/MAPK and the lipid kinase PI3K/AKT/mTOR pathways, are downstream signaling pathways for various oncogenic surface tyrosine kinases, such as IGF-1R or EGF receptor
The Cip/Kip family of CKIs regulate the actin cytoskeleton during neuronal migration by inhibiting the Rho signaling pathway
Pathway 1: Cholesterol synthesized in the ER is trafficked to the Golgi apparatus where it can be targeted to the mitochondria via the PAP7 protein for steroidogenesis
Virus infection and replication produces replication products, such as dsRNA, that are recognized and bound by RIG-I
Interferon response genes are coordinately upregulated relative to the rs17445836[G] allele of IRF8
Major components of FGF and HH signaling pathways
Schematic diagram of p75NTR-mediated signal transduction pathways
As described in the text that the BTB in the testis is constituted by integral membrane proteins of the: (i) tight junction (TJ): occludins, claudins, tricellulin, JAMs, and CAR; (ii) desmosome-like junction: desmogleins, desmocollins; (iii) gap junction (GJ): connexins; and (iv) basal ES: N-cadherins, nectins
Potential mechanisms regulating the duration of Erk (extracellular signal-regulated kinase) activation
Cigarette smoke-mediated oxidative stress activates the NF-Œ∫B pathway leading to acetylation of chromatin on pro-inflammatory genes thus increasing the accessibility of transcription factors leading to increased pro-inflammatory gene expression
A schematic presentation of the proposed TGF-β signaling alteration that promotes HNSCC in mice
Upon ligation and clustering by LDL, syndecan-1, -2 and -4 become enriched in detergent-resistant membranes and mediate the internalization of ligand via a non-clathrin endocytic route [,]
Survival signals generated by PI3K and PLD that target mTOR
HER2/neu is an orphan receptor that can be activated by overexpression or mutation of the transactivating domain (rat neu)
In response to sonic hedgehog secreted by the notochord, VEGF is secreted by adjacent somite leading to arterialization of the dorsal aorta
Representation of NF1 interactions with the Ras and PI3K pathways
Proposed model for the integration of anti-proliferative genomic and nongenomic 1,25D pathways via MAPK cross-talk through a classic VDR in human osteosarcoma cells
Lipopeptide antigens applied to intravaginal mucosal epithelium are taken up by mucosal resident antigen-presenting cells (APCs), especially DCs/pDCs, which are activated and migrate out of the mucosal inductive sites into the mucosal effector sites of draining lymph nodes where antigen presentation to T cells occurs, resulting in a strong local mucosal immune response
Toward better understanding of the mechanism of this hydroarylation reaction, the kinetic isotope effect studies were performed
Ligation of LPA to its G-protein-coupled receptors (LPA-R) LPA1‚Äì3 induces phosphorylation of EGFR through PKCŒ¥, Lyn kinase, MMP, and proHB-EGF pathway
Pathway for activation of Ca cycling proteins in cardiac myocytes during β-adrenergic stimulation
Schematic representation of the cellular mechanisms in endothelial cells mediating the antiangiogenic and capillary barrier actions of 2-ME
Ligation of HLA class I molecules by anti-HLA antibodies activates signaling cascades that result in EC survival and proliferation
Ketamine preferentially targets postsynaptic AMPA/NMDA receptors, while riluzole’s antidepressant effects occur through direct regulation, mostly at presynaptic voltage-operated channels and glia
Hypoxia signaling pathway in DM patients 4d post-CPB/C
Epidermal growth factor receptor (EGFR) pathway
The literature (see accompanying text) supports the involvement of cMet, IGF-1R and FGFR receptor tyrosine kinases in the autocrine and paracrine-stimulated growth of NSCLC, thereby conferring intrinsic resistance to EGFR TKIs
While adenocarcinoma is the dominant NSCLC histology sensitive to EGFR TKIs (), studies with NSCLC cell lines indicate more frequent autocrine signaling in squamous and large cell carcinoma-derived cells through FGF2, FGF9, FGFR1-IIIc and FGFR2-IIIc (; )
Cell-surface receptors transduce extracellular signals such as neurotransmitters and neuropeptides into the interior of the cell
The biosynthetic pathway for glutamate involves synthesis from glucose and the transamination of Œ±-ketoglutarate; however, a small proportion of glutamate is formed more directly from glutamine by glutamine synthetase
Nox1 is localized to cavaolae in the plasma membrane and endosomes
Schematic diagram depicting the mechanism of PTxB-mediated desensitization of CXCR4
Roles of ectonucleotidases in sequential activation of purinergic receptors
A) Proposed biosynthetic pathway for FkbH-dependent (2R)-methoxymalonyl-ACP formation; B) Proposed biosynthetic pathway for (2R)-methoxymalonyl-ACP formation during soraphen A biosynthesis; C) Biosynthetic pathway for (2R)-hydroxymalonyl-ACP formation during zwittermicin A biosynthesis; D) Biosynthetic pathway for (2S)-aminomalonyl-ACP formation during zwittermicin A biosynthesis
We recently found that sodium-butyrate (NaBu) profoundly decreased promoter I.3/II-specific aromatase mRNA expression induced by PGE2 or a surrogate hormomonal cocktail made of dibutyryl cAMP (Bt2cAMP) plus the PKC activator phorbol diacetae (PDA).
GDNF and SCF activate both the Ras/Erk and PI3K/Akt pathways, whereas SCF cannot signal via JAK/STAT pathway
Proposed schematic of Akt pathway control in the UMSCC47, UPCI-SCC90, and the SQ20B cell lines
B cell receptor (BCR) signals are initiated by SRC family kinases such as LYN, which phosphorylates immunoreceptor tyrosine-based activation motifs (ITAMs) on the BCR signalling complex (IgŒ± and Igβ)
Signaling pathways downstream of HVEM, LIGHT, and their binding partners are shown
Intracellular ascorbate (Asc) modulates redox-sensitive signaling pathways in microvascular endothelial cells during sepsis
Molecular targeting of the VHL pathway in clear cell renal carcinoma: Mutation of the VHL gene in clear cell kidney cancer results in increased accumulation of HIF and the resulting increase in transcription of downstream targets such as VEGF, Glut-1, and TGFŒ± (A)
A possible mechanism by which BMPs and estrogen regulate GNRH production by GT1-7 cells
This model is based largely on findings in zebrafish, plus Foxc1/2 and COUP-TFII results in mice (noted by dashed arrows)
C. elegans lacks the entire heme biosynthetic pathway and acquires heme in toto for incorporation into hemoproteins.
ER stress-induced signaling pathways that mediate autophagy
Cell signaling effectors downstream of EGFR may mitigate the efficacy of EGFR inhibitors by maintaining signaling activity to drive cell cycle progression and inhibit apoptosis
Dopamine Receptor Signaling: Genes differentially expressed in the NAC of LE vs
Synaptic Long-Term Potentiation: Genes differentially expressed in the NAC of LE vs
Actin polymerization and reorganization of the actin cytoskeleton occurs upon triggering of multichain immune recognition receptors (MIRRs)
Activation of caspase 3 and caspase-dependent apoptosis are caused by the initiator caspases, caspase 8 and caspase 9, as part of the extrinsic and intrinsic apoptotic signalling pathways, or by granzyme B
Anti-inflammatory, anti-oxidative and immuno-modulatory activities of gemfibrozil do not depend on PPAR-Œ±
Lineages are indicated with black arrows, inductive interactions are marked with green arrows, and inhibitory interactions are marked in red
In this very simplified depiction, three main pathways, the IIS, TOR and mitochondrial pathway, are indicated
IL-4 induces an alternate pathway for BCR signalling
Osteopontin expression is a specific outcome of alternate pathway signalling
Detection of proteins in the citric acid cycle (A) and in the fatty acid oxidation pathway (B)
The Stat1 signaling pathway and modulation by T
Upon ligation by LPS, TLR4 initiates the classical signaling pathway involving NF-kB as well as a second chain of reactions where cAMP is a major substrate
Lipid raft mediated bacterial uptake is initiated when FimH on UPEC ligates uroplakin 1a molecules found within lipid raft domains of the BEC plasma membranes
TLR4/cAMP signaling triggers rapid cytokine/chemokine secretion, inhibition of UPEC invasion, and UPEC expulsion from infected BECs
P. gingivalis activates the high-affinity conformation of CR3 through TLR2 inside-out signalling involving Rac1 and phosphatidylinositol 3-kinase (PI3K) (, ).
A proposed scheme of steroid-regulated cancer progression via Shc proteins
The progressive activation of IGF1-R signaling in the brain that accompanies aging leads to a naturally occurring TrkA to p75NTR switch
Integration of activated transcription factors with the upstream signaling network during CB1R-induced neurite outgrowth
A, Schematic diagram showing intra-cellular functions of the Bcl family of proteins
Schematic diagram of calcium signaling pathway initiated by melanoma contact to endothelium
Roles of the selected genes in the DSBR pathway
Model describing the regulation of protein synthesis by AMPK, Ca++ and Akt -signaling pathways
The most studied pathways of autophagy regulation, including mTOR-mediated suppression of autophagy, which is reversed by amino acid deprivation, rapamycin, or AMP-kinase (1), and the Beclin 1-class III PI3K pathways (2) are shown
Pathway generated by Ingenuity Pathways Analysis software genes differentially regulated by 400¬µM copper in HepG2 cells
Different views of the Akt pathway/network
(A) Stat5 signaling from cytokines that use γc... (B) Stat5 signaling controls the development of... (C) Stat3 is crucial to the development and fun...
Multiple regulatory loops exist within the EGF signaling cascade
This pathway was assembled using Pathway Architect (Stratagene) to identify potentially regulated transcription factors likely to be affected by PDGF receptor stimulation
The major biosynthetic activities used by proliferating tumor cells (synthesis of proteins, nucleic acids and lipids) are outlined in boxes
Extrinsic, receptor-mediated pathway illustrated on the left and intrinsic pathway illustrated on the right
EGFR signaling through the PI3K/Akt pathway
The Ret/GDNF pathway is restricted to the tip of the developing UB epithelium to insure progression of branching morphogenesis
TLR4 signaling occurs via a cascade of events
Left panel: Coactivator (e.g., SRC-3/AIB1) regulates the coordinate expression of multiple downstream genes (ER-responsive; E2F1-responsive; Her-2 responsive; NF-Œ∫B responsive; and protein kinase [P13K/AKT] responsive).
Induction of DSB causes unwinding and relaxation of torsional stress of the DNA double helix, which leads to local decondensation of chromatin and recruitment of the MRE11, RAD50 and NBS1 proteins (MRN complex), as well as BRCA1 to the DSB site
Chk2 is activated either by ATM (in response to DNA damage) or by ATR (in response to replication stress)
Canonical Wnt ligands bind to their cognate transmembrane receptors, comprised of a Frizzled family member and the LRP5/6 co-receptor
In both cell types, CXCR4, SDF-1, and MMP-1 are up-regulated compared to normal fibroblasts
Mitotic removal of cohesin in humans: In humans, cohesins (pink) are removed from chromosome arms in prophase in a Plk1-dependent pathway
Model showing the cleavage of the cohesion protein hRad21 by an unidentified protease in the nucleus and translocation of the C-terminal cleavage products to the cytoplasm early in the apoptotic pathway that amplifies the cell death signal in a positive feedback manner by activating more caspases
Phrenic long term facilitaion following acute intermittent hypoxia: schematic reperesentation of its cellular mechanisms and changes in relevant proteins following repetitive exposure to acute intermittent hypoxia
Schematic representation of TRAIL-R1/-R2 apoptotic signaling pathway
Nicotinamide, carnitine, resveratrol, and Sirtuins modulate tricarboxylic acid (TCA) cycle in mitochondria
To interrogate known interactions amongst the 25 lipid metabolic process genes that are co-regulated in PN and NN skin and the three transcription factors that show enriched numbers of binding sites in the promoters of these genes, we utilized Genomatix BiblioSphere to build gene interaction networks
Proposed model of the underlying mechanism by which NeuroD6 may bridge neuronal differentiation to survival
In ALCL cells, the TCR signalling pathway is non-functional, since NPM-ALK suppresses through STAT3 the expression of CD3ε, ZAP70, SLP76 and LAT by transcriptional repression and epigenetic silencing
A) In normal conditions, SIRT1 and FXR are associated with promoters of... B) In contrast, in metabolic disease states, FXR acetylation levels are...
Putative targets of common changes in gene expression with single and repeated IMO stress
NHEJ repairs DSB through an error prone mechanism available at any point during the cell cycle
The Moumen Lab showed that hnRNP K and p53 act as co-regulators
The topology of leukemia-related BCR-ABL pathway
A working model of PKA’s role in trastuzumab resistance
MyD88-dependent pathway: TLR4 recruits MyD88, which recruits IRAKs interacting with TRAF6, thereby activating IKKŒ±/β and phosphorylating IŒ∫B, resulting in NFŒ∫B nuclear translocation and initiation of gene transcription associated with innate immune responses and inflammation (left in Fig
Simplified representation of the complement cascade
The CD24-Siglec G (mouse) or -Siglec 10 (human) pathway discriminates between Pathogen-Associated Molecular Patterns (PAMPs) from Danger-Associated Molecular Patterns (DAMPs) by selective repression of the host response to DAMPs
Signaling pathways that lead from activated KIT and aggregated FcœµRI to mast cell responses
The emerging genetic network of the Wnt1 signaling pathway reveals the interaction between the Wnt1 and SHH pathways at three major steps of mDA development; i) ventralization and inhibition of alternate fates, ii) promotion of neurogenesis, and iii) DA phenotype specification and survival
Signaling and regulation of PRR-induced autophagy
Cisplatin (CDDP) enters cell by Ctr1 or diffusion and leads to DNA damage and cell death
Gene selection in the TGFß signaling pathway
Schema of major signaling pathways involved in renal development (for space and clarity, not all factors in each pathway shown)
Possible cross-talk between Nod2, TCR, Cd28, TLR and TNFR family members in regulating NF-Œ∫B
A schematic cartoon depicting the potential molecular mechanism by which shear stress regulates the activity of NF-Œ∫B
Viral infection elicits a variety of antiviral cellular responses
Mitochondria-dependent pathways of apoptosis in cerebral ischemia and reperfusion
Myeloma cells are addicted to IRF4 expression such that even a modest decrease in IRF4 levels leads to cell death
Schematic diagram of the cannabinoid receptor-dependent mechanisms whereby AEA leads to tumor growth suppression and/or cell death
Schematic presentation of the signaling pathway for LPS-induced PI3K/PKCŒ¥-dependent CHL1 expression in cultured astrocytes from early postnatal mouse cerebral cortex
Endotoxin binds to CD14 and Toll-like receptor 4 (TLR4) on the surface of monocytes and endothelial cells
Models of Merlin-dependent membrane receptor distribution in flies and mammalian cells
The current US Food and Drug Administration (FDA)-approved angiogenesis inhibitors for cancer therapy block vascular endothelial growth factor (VEGF) binding to the VEGF receptor (VEGFR2) (the inhibitor bevacizumab) or inhibit the tyrosine kinase activity of VEGFR2 (the inhibitors sorafenib and sunitinib)
TGF-β receptor signals through multiple signaling cascades
Schematic representation of the expression of cell cycle regulatory genes modulated by P
Osteoblast formation from mesenchymal progenitors is controlled by the canonical Wnt–β catenin and the BMP pathways
S. typhimurium interacts with intestinal epithelial cells from the apical surface and the effector protein, SipA, activates a novel signal transduction cascade that leads to the activation of PKC.
Raf activation signals through MEK/ERK pathway and Rb pathway
Multiple pro-inflammatory mediators in the tumor microenvironment increase the accumulation of MDS cells and enhance their immunosuppressive activity
Targets for lithium’s neuroprotective effects
VEGF binding to VEGFR2 on endothelial cells activates its Tyr kinase activity and results in autophosphorylation of the receptor at several cytoplasmic sites
Thrombospondin-1 (TSP1) binds to two receptors on endothelial cells that inhibit NO signaling
The NO/cGMP pathway is a signaling node for pro- and anti-angiogenic signaling
Schematic diagram summarizing alterations in molecules of the signalling pathway leading to protein synthesis in Lean and Obese Zucker rats after High force electrical stimulation (HFES)
The known JS-associated proteins are depicted in red and have been shown to localize to the basal body and/or primary cilium in at least some contexts
A schematic drawing illustrating the likely sequence of events in the seminiferous epithelium following Cd treatment (e.g., 3 mg/kg b.w.
The core components of the MAPK signaling pathway
A biochemical pathway of junction remodeling at the BTB, apical ES and hemidesmosome
Cross-talk between TCR and TGFβ signaling networks
Tobacco components stimulate cell surface receptors, such as members of the erbB family of receptor tyrosine kinases (RTK) and nicotinic acetycholine receptors (nAChR), which activate PI3K
Primary metabolic pathway for the elimination of alcohol
MATI/III and GNMT control DNA synthesis and hepatocyte growth
The omega-3 fatty acid docosahexaenoic acid (DHA), which humans mostly attain from dietary fish, can affect synaptic function and cognitive abilities by providing plasma membrane fluidity at synaptic regions
BDNF/TrkB signaling convergence on the MAP kinase pathway is implicated in both synaptic plasticity and learning and memory
Hypothesized regulation of the different routes of Ca2+ influx and/or release from stores by NTs, and its effects on intracellular Ca2+ levels
p38 signaling to the chromatin in muscle progenitor cells
"Cystoproteins” are proteins of genes mutated in cystic kidney diseases of humans, mice, or zebrafish
(A) This cartoon of arenal tubular epithelial cell shows how Wnt signali... (B) Stimulation of the primary cilium, e.g. by urine flow, results in in...
In the hedgehog pathway of vertebrates, upon binding of the Shh ligand to the patched (Ptch1) receptor, repression of the smoothened (Smo) receptor to be inserted into the cilium membrane is relieved, and posttranslational modification of the Gli transcription factors within the cilium induces both their activator (GliAct) and repressor (GliR) functions
There is a cross-talk between β-catenin and NF-Œ∫B pathways in Salmonella-epithelial interaction
As shown here, MAPK signaling through sequential steps involves TRAF6, TAK1, and MAPKK
Activation of TLRs though ligand binding leads to the recruitment of the adaptor protein MyD88 or TRIF
PI3K physically interacts with multiple TLRs as well as MyD88
Proposed schematic of ACh-induced neuroprotection
Network diagram of Sp1-interacting proteins
Schematic representation of Notch1 signaling pathway involved in ischemic regulation of cell proliferation in adult rat brain SVZ
The TGF-β-mediated signaling function in epithelia including the seminiferous epithelium of adult rat testes
Ingenuity Pathway Analysis annotates the differential proteins with biological and cellular functions and then calculates which of these biological and cellular processes are significantly overrepresented within the list of differential proteins
A) Gene array analyses were performed on liver fragments from control an... B) Schematic showing that several genes encoding factors required for IG...
Interestingly, the participation of at least four adaptor proteins containing Toll/IL-1 receptor (TIR) domains that can be recruited by activated TLRs results in important branching of the signal transduction and yields a significant flexibility to TLR signaling by allowing cross-talk with other pathways, including MAP kinase, PKR and Notch patways ()
CCM proteins form a molecular complex which interacts closely with cytoskeletal proteins and modulates inter-endothelial cell junctions
The genes associated AVM formation (shown in red) lie in the TGFβ superfamily signaling pathway
The wnt signaling pathway involvement in cancer and neurodegeneration
Simplified overview of the canonical Wnt/β-catenin signaling pathway
Signaling network model for heart valve development and remodeling
Binding of TGFβ to its cognate receptor initiates the signaling pathway
IR can promote a G2 arrest in cells with and without wild-type p53 at least in part by increasing Wee1 and Chk1 activity
A gene program of neutrophil recruitment and tissue injury based on gene expression and in vitro data
A simplified diagram of the angiogenesis pathway with anti-angiogenic targets and select compounds exploiting them
Target genes, Gnas, Got2 and Snord32a, following tenofovir exposure of primary osteoclasts
Schematic diagram of TK-mediated signaling pathway promoting HaCaT keratinocyte migration
HDL promotes cholesterol efflux via ABCA1 and ABCG1 and these transporters modulate the fluidity of the plasma membrane as well lipid raft formation
These results and previous studies () demonstrate that two pathways present during valvulogenesis are also active in post-natal heart valves
When an estrogen molecule binds to an estrogen receptor, the hormone-receptor complex then moves to the nucleus, where it binds to DNA and initiates transcription
AITC metabolism through the mercapturic acid pathway
Schematic representation of the postulated signaling of MAP kinase pathway in proliferating or differentiating HL60 cells
Schematic representation of VDR-dependent and auxiliary pathways that lead to deltanoid-induced monocytic differentiation of myeloid leukemia cells
Coupling between Akt-mediated cellular energy metabolism, cell survival and proliferation
Mammalian target of rapamycin (mTOR) is an important checkpoint kinase that transmits signals related to amino-acid sufficiency and protein synthesis
The cilium/basal body may function as a regulatory switch to control the balance between the canonical and noncanonical Wnt pathways
Farnesol induces ER stress and activation of the unfolded protein response
Activation of the NF-Œ∫B signaling pathway by farnesol is related to ER stress
The insulin signaling pathways of mammals, D. melanogaster and C. elegans, respectively are shown from top to bottom.
The Hexosamine signaling pathway terminating in the enzymes of O-GlcNAc cycling lies at the center of many of the major nutrient sensing pathways (p38 MAPK, Insulin-AKT, mTOR, AMPK and SirT1)
As a modulator of signaling, endocytosis, transcription, translation and protein stability, the HSP may coordinately regulate nutrient sparing and salvage
In addition to the GnRH receptor, RT-PCR analysis of RNA isolated from cultured GT1-7 neurons revealed the expression of mRNA for 5-HT2 Gq-coupled receptors, Gs-coupled 5- HT4 and 5-HT-7 receptors and 5-HT1A Gi-coupled receptors
Schematic of the low-density lipoprotein receptor-related protein 5 (LRP5)–5-hydroxytryptamine (5-HT)–osteoblast pathway observed by Yadav et al
Unanswered questions regarding the low-density lipoprotein receptor-related protein 5 (LRP5)—5-hydroxytryptamine (5-HT)—osteoblast pathway.1) What is the ligand for LRP5 within enterochromaffin cells?2) What is the molecular pathway between LRP5 and tryptophan hydroxylase 1 (Tph1) within enterochromaffin cells?3) Does LRP5-mediated 5-HT synthesis by enterochromaffin cells have any local effects on the gastrointestinal (GI) tract?4) How are LRP5-mediated changes in circulating 5-HT levels transported to bone cells (i.e
GSK3 regulation of STATs, Smads, β-catenin, and NFAT
A nuclear phosphoinositide-mediated stress response pathway
A. Dopamine D1 and D2 receptor homooligomers modulate adenylyl cyclase activity and cAMP accumulation in opposite ways through Gs/olf and Gi/o proteins, respectively (left panel).
TGF-β decreases intracellular GSH by suppressing the expression of glutamate cysteine ligase (GCL), the rate-limiting enzyme in de novo GSH synthesis
The results represent mean fold-change in gene expression in response to luteolin treatment relative to EtOH control
Increased synaptic activity stimulates glutamate release which, in turn, activates NMDA receptors
The colorectal cancer (CRC) stem cell model
Model of Ras signaling in early B cell development
This model illustrates the circadian rhythm in chicken cone photoreceptors
Overview of chemotactic signalling in neutrophils
Signaling through TNFRs, IL1R, TLRs and TCR leads to the activation of NF-Œ∫B
DAP-type PGN binding causes multimerization or clustering of PGRP receptors
Summary of potential mechanism by which altered OC nAChR activity may drive structural and functional changes observed in cochleae of Œ±9 null mice
Schematic diagram of autophagy signaling pathway in C
LT-IIb-B5 activates the TLR2/TLR1 heterodimer and induces NF-Œ∫B-dependent production of proinflammatorry cytokines (; ; )
Using gene-association files from the Kyoto Encyclopedia of Genes and Genomes Consortium, genes significantly regulated by urothelial carcinoma are depicted in a functional map annotator pathway profiler created by Pathway Studio
Transcriptional regulation of the differentiation of Th1 cells
Transcriptional regulation of the differentiation of Th2 cells
(A) Suggested signaling of the early stages of 1,25D-induced monocytic d... (B) Later stages of 1,25D-induced differentiation. This figure illustrat...
Binding of IFN-α/β to the IFN receptor stimulates the phosphorylation of STAT1 and STAT2
Schematic representation of AURKA interactions
Redox signaling responses in DCs and T cells during T cell activation
Reactive oxygen species (ROS) induced damage in diabetic endothelial cells
Intracellular signalling pathways for migration
a. Other than general functions of the fatty acid-binding protein (FABP), adipocyte FABP (A-FABP; FABP4) interacts with hormone-sensitive lipase (HSL) to potentially modulate its catalytic activity and integrates several signalling networks that control inflammatory responses potentially through JNK/inhibitor of kappa kinase (IKK) and insulin action in the adipocyte.
The IL-17R complex is composed of IL-17RA and IL-17RC
Portrayed here is a molecular pathway analysis of genes regulated in the mouse nucleus accumbens by a direct infusion of the HDAC inhibitor MS-275 after chronic social defeat stress
Comparison of gene expression in peripheral blood cells stratified by the C8orf13-BLK variants rs2736340-rs13277113 heterozygote versus homozygote in SSc demonstrates alterations in B Cell Receptor Signaling Pathway (A) and NFŒ∫B Signaling Pathway (B)
Schematic of how the PI3K-AKT and MEK-ERK pathways regulate apoptosis in EGFR driven cancers
The Intrinsic pathway is triggered by various stresses including hypoxia/ischemia, growth factor deprivation, and cell damage
Proposed signaling pathway by which AngII inhibits the activity of ROMK channels in the CCD from LK-fed rats
The stimulation of cells to increase intracellular Ca2+ leads to activation of MLCK and phosphorylation of myosin II RLC
Specific noncoplanar PCBs may directly activate the ryanodine receptor (RyR) causing release of Ca2+ from endoplasmic reticular (ER) stores
Estrogens stimulate ERŒ± complex formation with cytoplasmic signaling proteins like MNAR, cas, and c-SRC
The Intrinsic pathway is triggered by a disruption in the BAX:Bcl-2 protein ratio at the mitochondrion
Entry into an ICL repair pathway depends on the mode of recognition
Using the influenza A virus lifecycle as a guide (), the candidate proteins from the human and fly screens were placed at the position most likely to be relevant to the virus using a database of annotations from Gene Ontology, KEGG, Reactome and OMIM (see methods)
GPCR signaling can be mediated by receptor-interacting proteins
BMP/TGFβ signaling in vivo is mediated by either the Smad pathway (canonical) or the Non-Smad (non-canonical) pathways
An intricate gene regulatory network controls OL differentiation
Schematic representation of the current understanding of PELP1 signaling pathway
(A) IL-7 signaling is through the Jak-Stat pathway
Insulin and IGF1 signaling pathway to promote glucose uptake by GluT3 in neurons (shown) or GlutT4 in muscle (not shown)
A putative mechanism by which the UPS acts downstream of BDNF/TrkB signaling to ultimately regulate Œ±-synuclein aggregation
Hypothetical function of mT1-mmP homodimer and heterodimer formation on proteolytic activity, cell migration and proliferation: The hemopexin (PeX) domain of mT1-mmP interacts with CD44 or an unknown protein (heterodimer) at the cell surface, which signals for cell migration through maPK, PI3K and rac pathways, possibly involving initial activation of receptor tyrosine kinases (rTK) and ras
Sphk, sphingosine kinase, S1PP, sphingosine-1-phosphate phosphatase, Lyase, sphingosine-1-phosphate lyase
Bradykinin and kallidin, generated by the action of plasma or tissue kallikrein on precursor high-molecular-weight (HMW) or low-molecular-weight (LMW) kininogen, are ligands of the B2R
(A) In physiological hypertrophy, T3 binding to cytoplasmic TRŒ±1 or growth factor binding to receptor protein tyrosine kinases (RPTK) activates PI3K isoform p110Œ± through direct interactions with the p85 subunit of PI3K
All transcripts from ligands through transcription factors (except LimK) depicted in the model exhibited a statistically significant increase in conditioned media at 24 or 48 hours compared to the level at the beginning of the study
Four pathways including three classical immune signaling pathways (Toll, Imd, Jak-STAT) are responsive to infection by different viruses (blue text) based on studies in both Drosophila and mosquitoes (italics)
Hypothetical model of NKT cells in immune-mediated pregnancy loss
Autophagy regulation in response to stress
Regulation of autophagy induction in yeast and mammalian cells
Wwox-partner protein interactions in signal pathways are affected by absence or reduction of Wwox expression
Schematic diagram of the activation of membrane-bound GCs by intracellular signals
Depicted are the different stages of mouse embryonic pancreas development in vivo (left), with darker shaded areas representing developmental intermediates that have been recapitulated in the directed differentiation of pluripotent stem cells (PSCs) to pancreatic beta cells in vitro (center)
Sonic Hedgehog, Wnt and TGF-β signaling pathway gene expression in CpG late treated macrophages [; ; ; ], see discussion
TNFSFR and NF-Œ∫B signaling activation during macrophage activation: CpG late responses
A number of intrinsic and/or extrinsic stimuli lead to the activation of specific cell signaling pathways in skeletal muscle in muscular dystrophy
Two major PCP pathways have been defined: The Fat pathway (red) and the Core PCP pathway (blue)
The PI3K-Akt pathway negatively regulates LPS signaling and gene expression in mouse macrophages by inhibiting the activation of MAPKs
Three pools of GSK3 are hypothesized to exist
TGF-β can be liberated from latent complexes by αvβ6 integrin, calpain, cathepsin D, chymase, elastase, endoglycosidase F, kallikrein, matrix metalloproteinase 9 (MMP-9), neuraminidase, plasmin or thrombospondin 1
Mechanisms of HSV-1-mediated antagonism of TLR-dependent, anti-viral pathways
Cytokine signaling through the JAK/STAT pathway
Neurotrophin actions on the endothelial cell
Model of CD62L regulation by T-cell receptor (TCR) stimulation and γc-cytokines
The rat NF-Œ∫B signaling pathway RT2 Profiler PCR Array was used to examine the expression of 84 pathway-focused genes and the resulting gene expression values were analyzed by one-way ANOVA and only genes that demonstrated a > 2-fold change with P < 0.05 in the contrast comparison of expression values from experimental treatment cells and mock infected cells were considered differentially expressed.
The canonical Wnt/β-catenin pathway (modified after ())
Schematic of a signaling cascade activated by opiates
Simplified schematic of the IgE receptor (FcŒµRI) signaling pathway
Simplified schematic of the T cell receptor signaling pathway
Cellular pathways involved in the synthesis, folding, secretion, trafficking, clearance and neurotoxicity of the prion protein
Either bacteria (1) or ligands for TLR 1, 2, 4, 6, and 9 receptors (2) are sensed by APC and activate a signaling pathway (3) that leads to the activation of the transcription factor NF-Œ∫B and p38 MAPK (4) to mediate the production of TL1A by APCs (5)
Certain bacteria (P. gingivalis, M. tuberculosi, B. anthracis) bind CD14 and induce TLR2-dependent inside-out signaling, mediated by Rac-1, phosphatidylinositol-3 kinase (PI3K), and cytohesin-1 (Cyt-1), leading to activation of the ligand-binding capacity of CR3.
Antigen specific T cells are primed in secondary lymphoid tissue and driven into the Th17 developmental pathway in the presence of IL-6 and TGF-β
Aldosterone is synthesized in the zona glomerulosa of the adrenal gland in response to angiotensin II (Ang II), adrenocorticotropin (ACTH), potassium, and lipid soluble factor(s) produced in fat tissue ()., The classical genomic pathway of aldosterone action involves binding to cytosolic MRs and subsequent translocation to the nucleus, gene transcription, and translation of effector proteins involved in regulating sodium and potassium balance across renal tubular epithelial cells., Aldosterone also exerts rapid, non-genomic effects that mediate maladaptive tissue remodeling throughout the cardiovascular and central nervous system, further perpetuating the CMS, insulin resistance, and the hypertensive state.
ZIP4 overexpression causes increase of IL-6 expression and secretion through phosphorylating CREB, which in turn activates STAT3, and leads to increased cyclin D1 expression, resulting in increased cell proliferation and tumor progression
Cancer cells and stromal cells secrete VEGF, which via VEGFR2 stimulates expression of ATX and extracellular LPA production, as well as mRNA levels for LPA1 receptor
In medium spiny neurons of the dorsal striatum, excitatory afferents from the cortex and dopamine fiber arising from the substantia nigra converge
Human telomeres consist of many kilobases of TTAGGG repeats, with a G rich leading strand and a C rich lagging strand
In the event of single stranded breaks or fork stalling ATR is activated and RPA (Replication Protein A) binds to the exposed strands
Plants possess plasma-membrane-localized pattern recognition receptors (PRRs) that consist of an extracellular leucine-rich repeat (LRR) domain and a cytoplasmic serine/threonine kinase domain
The general synthetic route to the racemic vinyl, ethyl, n-propyl, n-butyl, i-butyl, 2-propenyl, allyl, ethynyl, and 1-propynyl mevalonate lactone analogues (1a–e, g, i–k) is shown in
Shown above is a schematic of the cross talk between the epicardium (blue) and myocardium (red) during the early stages of coronary development
In the progression of colon cancer, genetic alterations target the genes that are identified at the top of the diagram
As a negative feedback mechanism, radiation-induced TGF-β, elevates the expression of SMAD7, which blocks the activity of this pathway
Routes of interaction between epoxyeicosanoid and endocannabinoid signaling pathways
Signals delivered by the engagement of the T-cell receptor (TCR; Signal 1) and co-stimulatory molecules (CD28; Signal 2) induce different signaling pathways that result in the activation of multiple transcription factors
Signals delivered by the engagement of the TCR (signal 1) and costimulatory molecules (CD28; signal 2) induce different signaling pathways that result in the activation of multiple transcription factors
(A) In wild-type testes, UPD is expressed in hub cells (green) and activates JAK/STAT signaling in adjacent germline stem cells (GSC, dark pink) and cyst progenitor stem cells (CPC, blue)
Regulation of the mTOR pathway by nutrients (amino acids, glucose), stress and insulin/IGF-1
A schematic diagram of molecular interactions stimulated by HMW-HA
An early step in the initiation of allergic airway inflammation is the activation and maturation of antigen-presenting dendritic cells in response to thymic stromal lymphopoietin (TSLP), an interleukin-7-like cytokine that is produced by airway epithelial cells, fibroblasts and mast cells
At later stages of 1,25(OH)2D3-induced monocytic differentiation there is increased expression of the transcription factor C/EBPβ
Saturated FFAs accumulate in the ER, which leads to disturbance of ER function and induction of an ERstress response, mediated by the phosphorylation and activation of two ER-resident kinases, IRE1Œ± and PERK
a | In conventional T cells, mTOR integrates the TCR and CD28 signals that are necessary to pass two checkpoints of T-cell activation
Main targets of RhoA and ROCK, involved in organization of the cytoskeleton
Metabolic pathways active in proliferating cells are directly controlled by signaling pathways involving known oncogenes and tumor suppressor genes
Frequent amplification and overexpression of multiple EGFR-family-signaling components in non-small cell lung cancer (NSCLC)
Crosstalk between intracellular signaling pathways in female reproductive behavior
Schematic presentation of PI3K-Akt signaling
Schematic presentation of Akt-mTOR signaling
The decentralized model of endothelial mechanotransduction by shear stress
Model for the mechanisms of retinoid induction of NIS expression in MCF-7 cells
Non-genomic estrogen mediated endothelial pathways of vascular relaxation
Non-genomic estrogen mediated mechanisms of VSM contraction
The CD28 costimulation, IL-2 signaling, and mTOR pathway regulate Otub1 and GRAIL expression, controlling proliferation in primary naive CD4 T cells
The induction of autophagy by various stimuli (e.g.
Multiple inputs regulate activity of the TOR/Raptor/Lst8 complex (TORC1) through redundant upstream signaling pathways
Mammalian autophagy proceeds through a series of steps, including initiation at the PAS (phagophore assembly site), elongation and expansion of the phagophore, closure and completion of the autophagosome, autophagosome maturation via docking and fusion with an endosome and/or lysosome, breakdown and degradation of the autophagosome inner membrane and cargo, and recycling of the resulting macromolecules
Autophagy is regulated by a complex signaling network of various stimulatory (arrowheads) and inhibitory (bars) inputs
One branch of mTORC1 activation is mediated by the class I phosphoinositide-3 kinase (PI3K), Akt (also known as Pkb) and the tuberous sclerosis complex (TSC)
(A) S6K1 phosphorylation by mTORC1 triggers a n... (B) Deptor can have oncogenic and tumor suppres... (C) The 2 most important tumor suppressors, nam...
The signaling complexes induced by TNFŒ± to mediate NF-Œ∫B activation, apoptosis and necroptosis
Minimally oxidized LDL induces TLR4-dependent lipoprotein uptake by macrophages
Cross-talk between the hexosamine biosynthesis pathway, O-GlcNAc modification of proteins, signaling events downstream of insulin action, and glucose-induced adipocytokine secretion
Schematic of the kynurenine pathway with relevant regulatory components, summarizing gene expression and metabolite changes previously identified for schizophrenia in the frontal and anterior cingulate cortex
Molecular cascades of fear memory stabilization in the amygdala
The Brx-mediated osmotic stress-activated signaling system and its implications for the immune response
Opposing influences on Foxo cellular localization and transcriptional activity
Simplified scheme of early FcŒµRI-mediated signaling events
Convergence of Pathways in TLR and IL-1R SignalingUpon activation, the IL-1 receptor dimerized with the IL-1 receptor accessory protein
The contribution of TGF-β signaling to regulation of BCL-2 family members is included alongside known apoptosis pathways functional in germinal centres
a | MDM2 and SIRT1 negatively regulate p53 and prevent upregulation of p53 under normal conditions
The PLCβ – G protein signaling pathway showing how the binding of an extracellular to a transmembrane GPCR will activate a G protein heterotrimer whose G α or G βγ subunits can bind to and activate PLC β
A. Under physiological conditions, mTOR controls multiple downstream effectors, such as S6K/S6 and 4EBP1/eIF4E, which regulate protein synthesis and other processes related to cellular growth, proliferation, metabolism, and survival.
Glucose is oxidized to pyruvate through the glycolytic pathway
Schematic representation of EDA signaling
A simplified model of the signaling pathways regulating radiation-induced bystander effects
Potential targets for inhibition are depicted in light gray boxes
PI3K converts the lipid PIP2 into PIP3 (Phosphatidylinositol (3,4,5)-trisphosphate), which localizes AKT to the membrane
Simplified scheme of the cAMP pathway and the regulation of renin synthesis and release
Schematic representation of the two major transduction pathways of apoptotic signalling
Key role of the PI(3)K/Akt signalling in the cumulo-oocyte complexe survival
Schematic diagram of the signaling pathway that connects store-operated Ca2+ entry with NFAT-dependent gene transcription in T cells
A hypothetical model linking multiple biological pathways in the development of SS-like disease based on differentially expressed genes identified in lacrimal glands by global microarray analyses
The kinases indicated with an open box appear not to be involved
Signal transduction pathways and crosstalk activated by insulin/IGF-1 receptor and GPCR systems
In our previous work we demonstrated that GLP-1 or Exendin-4 increased cAMP production
Schematic drawing of the signal transduction pathways involved in human gingival fibroblast (HGF) migration including the possible effects of nicotine on these pathways
Examples of pathways that may be activated by EP2R and EP4R
Multi-component nature of TGFβ and Wnt Pathways
In normal myeloid progenitors (left side schematic), miR-24 is repressed by Runx1
Sites of action of curcumin on cancer cells
High-affinity ligands for the AR are shown in green boxes
A schematic representation of the DNA damage and replication checkpoints in various organisms
Posttranslational modulation of FoxO proteins is associated with intricate cellular signal transduction pathways
High levels of phosphotidyl inositol-protein kinase C signaling in the PFC markedly impair PFC function at the behavioral and cellular levels
HES1 usually functions to inhibit differentiation in normal cells and tumors
Effect of estrogen (E2) on endothelial nitric oxide synthase (eNOS)
Wnt signaling is a complex pathway, believed to be involved in the regulation of divergent processes, including the maintenance of pluripotency and commitment to differentiation
GM-CSF initially binds to the low-affinity GM-CSF receptor α chain (α), followed by association with the affinity-enhancing β chain (β) and constitutively associated Janus kinase 2 (JAK 2) resulting in assembly of a dodecameric structure signaling complex.At low concentrations of GM-CSF (<300 pg/ml), as are normally present in normal healthy tissues, signaling occurs through Ser585 of the β chain and results in myeloid cell survival and GM-CSF stimulated expression of some GM-CSF-dependent TLR-4 signaling pathway components, CD14, RP105, and IRAK-M (dotted lines); other components are not affected by GM-CSF.
The SIRT1-AMPK metabolic control network
Receptor tyrosine kinases (RTKs) and immunoreceptors such as the T cell receptor (TCR) activate phospholipase Cγ (PLCγ), which hydrolyses phosphatidylinositol-4,5-bisphosphate (PIP2) releasing inositol-1,4,5-triphosphate (InsP3) and diacylglycerol (DG)
TLR/IL-1R pathway, IL-1R, and all TLRs (except TLR3) signal through the adaptor protein MyD88, leading to NF-κB activation and transcription of proinflammatory cytokine genes
The genes shown in solid black have previously been reported to be dysregulated through DNA methylation, histone modifications, miRNA expression and combinations of these mechanisms
Matriptase-2 prevents hepcidin overexpression by degrading hemojuvelin (HJV), which acts as a co-receptor for BMP to promote Hamp gene expression (panel A)
Signaling pathways mediating the dual roles of senescence-associated inflammatory cytokines in cancer development
To identify differential distributions of KEGG pathways, we performed a FatiGO+ analysis with the two lists of genes up-regulated gene during endometrial receptivity of the natural and stimulated cycles
Analysis of a protein interaction network in the context of the T-cell pathway
Structuring protein interactions around familiar canonical pathways provides intuitive visualizations
Proteins and interactions from HPRD (small fonts) that are connected to the canonical pathway model are: (left) integrated directly into the signaling pathway image with one protein selected and its interactions highlighted; (right) structured around a user-constructed model; different classes of proteins have different appearances: experimental proteins are colored yellow, kinases are drawn as hexagons and receptors as irregular stars; several experimental proteins are not known to be connected to the pathway and are therefore located in the lower right corner
Subjecting cells to HPC or stimulation with insulin results in ILK-AKT-dependent downregulation of miR-199a-5p and upregulation of its targets Hif-1Œ± and Sirt1
(1) Unmethylated Lefty gene permits high-level expression of Lefty by human embryonic stem cells (hESCs)
Multiple strategies are currently being employed and explored to inhibit the pathological activation of this pathway
The intrinsic pathway is deregulated in cancer
48 genes clustered into two major networks associated with immune dysregulation
In this summary of approaches used to date to identify candidate genes for AD, the first consideration is the complex pathology of AD (panel A), which includes defects and damage at the epithelial barrier, and penetration of allergens, microbes, pollutants and irritants into the epidermis and dermis, ultimately interacting with antigen presentation cells (i.e., Langerhans cells and dermal dendritic cells).
ER and SR interactions within mammalian cells
Anabolic and catabolic pathways regulating skeletal muscle mass
8 statistically significant inter-signature connections were identified relating 6 of the ten signatures [inset] based on genetic overlap (common genes between signatures) after adjusting for the varying background of genes of the different expression platforms (adjusted p<5pct; cumulative hypergeometric distribution)
We evaluated the connectivity of the 54-gene breast cancer network signature to itself through permutation resampling of the PPI controlling for hubness
Various agonists or stimuli bind and activate their respective receptors, leading to the activation of the SK/S1P pathway by both known and unknown mechanisms
(A) Differentiation of mesenchymal stem cells i... (B) Embryonic stem cells differentiate down a n... (C) Keratinocyte stem cells differentiate into...
Two models for coupling the circadian clock to the cell cycle/checkpoint response
Major characteristic pathways activated by VEGF-A/VEGF receptor-2 and in part distinct from pathways induced by the IL-1 and EGF receptors in endothelial cells are shown
Illustration of different mechanisms of MUC1 and MUC4 for the repression of apoptosis
Results of a Pathway Studio® analysis of direct relationships between the components of the protein-bound fraction of renal cyst fluid
Model of revitalization of a diastemal bud
Model of neuronal ischemic preconditioning
Pathway analysis using all altered genes and proteins
A simplified representation of oncogenic signaling cascades in pancreatic cancer
Pathway analysis of disease associations in the hypothalamus (genes regulated at p<0.001; fold change > ¬±1.5)
Displayed is the signaling pathway associated with insulin-mediated activation of endothelial nitric oxide synthase (eNOS)
Initiation: Normal, quiescent endothelium does not express functional TF
Transcriptional regulation by E2F complexes modulates cell-cycle control, cell fate, and survival
Signaling through the PI-3 Kinase-Akt pathway
Possible mechanism of regulation of SIRT1 and AMPK pathway by CD38 inhibition
Ligand binding to CRF1 receptor activates at least three GŒ± subunits (Œ±s, Œ±i and Œ±q) of G-protein resulting in stimulation cAMP production by adenylate cyclase (AC) with subsequent cAMP-induced phosphorylation of CREB and activation of the cAMP-responsive element (CRE)
Schematic of IGF-I activation of a signaling pathway to mTOR
A complex series of phosphorylation events and other protein interactions regulate hamartin/tuberin and activity of the mTOR kinase
Diagram of PDGF-D cross-talks with other pathways
Functional capacity and muscle mass are regulated by contractile and activity and the associated calcium signaling
TORC1 integrates intra- and extracellular environmental cues through discrete signaling modules that sense and relay diverse inputs to a central “signaling core” (in green)
The diagram represents the genetic interactions in the TOR signaling network that execute lifespan extension in yeast, worms, flies and mice
While the cell death pathways regulated by DOX are highlighted in red, the pro-survival effects of WISP1 are shown in blue
Schematical overview of the signaling pathway mediated by MC1R
Schematical overview of the signaling pathway mediated by OA1
SIRT1 is recruited to target gene promoters and regulates the acetylation state of histones, transcription factors, and other chromatin-associated proteins in an NAD+-dependent manner
Carbohydrate metabolism and fermentation in tumor cells
Cocaine self-administration depletes dopamine levels in the nucleus accumbens but results in a compensatory upregulation of the PKA–CREB–dynorphin signaling pathway
Role of ROS in TNF-Œ± induced endothelial dysfunction
Signalling through growth factor receptors can activate the PI3K/Akt/mTOR pathway and the JAK3/STAT5 pathway
Peroxisome proliferator-activated receptor-γ (PPARγ) expression can be regulated at the transcriptional level by tumour-necrosis factor-Œ± (TNFŒ±) (arrow 1) through the activation of nuclear factor-Œ∫B (NF-Œ∫B) and activator protein-1 (AP1), which negatively regulate PPARγ expression‚Äì
a |  In small adipocytes (lean condition), insulin promotes free fatty acid (FFA) esterification into triglycerides (TG, schematically represented as the three-carbon glycerol backbone with three acyl fatty acid chains (wavy lines)) through stimulation of glucose transporter type-4 (GLUT4)-mediated glucose uptake
EGFR Signaling Pathway and Several Mechanisms of Resistance to EGFR-Targeted TherapiesAbbreviations:EGFR: epidermal growth factor receptorK-Ras: v-KI-RAS2 Kirsten rat sarcoma viral oncogene homologH-Ras: v-Ha-ras Harvey rat sarcoma viral oncogene homologPTEN: phosphatidylinositol phosphatasemTOR: mammalian target of rapamycinmAbs: monoclonal antibodiesTKIs: tyrosine kinase inhibitors
There are several potential avenues through which ER function is linked to inflammatory signaling
On the cytoplasmic face of the ER, dolichol phosphate is modified by glycosyltransferases, which utilize nucleotide-activated sugar donors, to form Man5GlcNAc2-PP-Dol
Simplified scheme of signaling pathways required for maintenance of pluripotency of mESC (top panel) and hESC (bottom panel)
Genetic Alterations in Glioblastoma Occur Frequently in 3 Cellular Signaling                         Pathways
Cellular apoptosis pathways and intervention by both cellular anti-apoptotic proteins and viral proteins encoded by oncolytic Ad, HSV and VV
Drug-induced DNA damage may be repaired by various DNA repair pathways, or apoptosis may be triggered as a result of attempted repair of platinum-induced damage by the Mismatch Repair pathway
(A)Schematic model showing the role of PKCŒ¥ in neurotoxin-induced neuronal apoptosis
A schematic of Hh pathway signal transduction derived from developmental and cancer models
Response of p53 to DSBs generated by ionizing radiation
Crosstalk between the PI3K/AKT pathway and p53 activation: Potential stratagies for combined radiosensitization
The protein components of the pheromone response network constructed by the PCST approach
Potential islet GPCRs and their downstream signaling pathways
Cumulative pathological and experimental evidence indicates that cell type-specific characteristics modulate the vulnerability of specific neuronal populations to mutant huntingtin expression
Ingenuity Pathways Analysis software (http://www.ingenuity.com) was used to depict potential signaling pathways between (A) high-abundance and (B) low-abundance, GŒ±q-regulated gene products.
The TGF-β ligands signal through the type I and type II TGF-β receptors
Possible interactions between cholinergic and eCB signaling in the toxicity of organophosphorus anticholinesterases
The roles of cGMP and S-nitrosylation in NO-based signaling (A) and enzymatic protein denitrosylation mediated by the S-nitrosoglutathione reductase (GSNOR) and thioredoxin (Trx) systems (B)
Endotoxin binding: Schematic overview of the LPS, LBP, CD14 and TLR-4 signal transduction pathway
General overview of BDNF and GDNF signaling mechanisms
Panel 1: Inflammation, hypoxia and reactive oxygen species (ROS) up-regulate expression of pro-lymphangiogenic factors VEGF-C, VEGF-D and VEGF-A produced by both tumor neoplastic and tumor-associated stromal cells (e.g.
Hypothetical model of crosstalks between EPCR, PAR-1, S1P1, and Tie2
Transcription factors, such as nuclear factor kappaB (NFŒ∫B), ŒîFosB, cyclic AMP response element binding protein (CREB), and myocyte enhancing factor-2 (MEF2), play a role in regulating dendritic spines, and can be activated by a variety of signaling pathways
Cellular pathways leading to upregulation of COX-2 in neutrophils
(A) Upon activation by signaling through the T-cell receptor and co-stim... (B) C. albicans is recognized, taken up by antigen presenting cells (APC...
From gathered evidence presented in this article, HS is involved in several key functions regarding cancer progression
Interplays between various posttranslational modifications
Schematic overview of costimulatory receptors and their ligands
Chemoattractant stimulation promotes the F-actin-dependent recruitment of the Sca1 complex to the plasma membrane and the subsequent activation of the RasC-TORC2-PKB/PKBR1 pathway at the leading edge of chemotaxing cells
Lineage relationships of cells originating in the otocyst
Schematic of the nicotinic-alpha7nAChR mediated activation of Jak2 neuroprotective pathway
DCs are differentiated in bone marrow from hematopoietic progenitor cells (HPC) alongside two major pathways
Hsp70 is thought to promote survival and block apoptosis through interactions with multiple steps in the pathway
Signalling pathway heatmap of interactions defined by the TCGA ()
Proposed model for macrophage inhibitory cytokine-1 (MIC-1)-mediated signaling events that promote actin cytoskeleton rearrangement
Toll-like receptors (TLRs) signal through proximal adaptors
Diagram showing some key features of AQP2 recycling
Wnt1 mRNA in the rhombic lip is graded with the highest expressors giving rise to hRPe beginning at ~E8
Nucleic acid-sensing TLRs, which include TLR-3, -7, -8 and -9, are localized to endosomal compartments
Schematic representation of key targets and pharmacological agents that inhibit MAPK signaling proteins
A. TLR2 and 4 recognize bacterial lipoprotein (BLP) and lipopolysaccharide (LPS), respectively, and signal from the cell surface via the adaptor MyD88 to activate proinflammatory cytokines including TNFŒ± and IL-6.
Receptor activation upon binding of Wnt 1 or Wnt3A leads to stabilization of β-catenin which localizes to the nucleus where it associates with transcription factors and activates transcription of genes involved in proliferation and tumor progression
Receptor activation by Wnt leads to the recruitment of Dsv, resulting in the activation of Rac1 and RhoA, both of which are involved in cytoskeletton remodeling and establishment of an EMT phenotype
Binding of Wnt5A to ROR2 leads to the activation of Ca2+ and PKC, which in turn stabilizes Wnt5A mRNA and increases its secretion
During cold exposure in brown fat, (i) norepinep... (ii) Activate... (iii) Fatty a... (iv) Norepine... (v) phosphory... (vi) Within m... (vii) Under c...
Arachidonic acid is a polyunsaturated fatty acid that constitutes the phospholipid domain of most cell membranes and is liberated from the cellular membranes by cytoplasmic phospholipase A2 (PLA2)
Multiple cellular signalling pathways mediate the effects of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) on the regulation of epithelial tumour cell proliferation, survival, and migration and invasion
Pro-inflammatory prostaglandin E2 (PGE2) and/or B4 LTB4 promote angiogenesis on at least two levels
A model for molecular pathway for arterial, venous and lymphatic cell fate determination in vertebrate embryo
Evolving concepts of signaling pathway activation
Proposed DAP12 signaling pathway in macrophages and osteoclasts
Overview of the Taxol biosynthetic pathway
Early bifurcation of the Taxol biosynthetic pathway following the 5α-hydroxylation step, and involving the taxoid 13α- (T13OH), 10β- (T10OH), 14β- (T14OH) and presumptive 9α- (T9OH) hydroxylases
The point of inhibition of the two classes of inhibitors, protein synthesis inhibitors and ROS, identified from high throughput screens are indicated
Multiple levels of regulation control stress-induced differentiation in Toxoplasma
a |  In the classical model for seven-transmembrane receptor (7TMR) activation, signalling is mediated by G proteins and desensitization is mediated by β-arrestins
Model for potential functions of intracellular peptides
1). PEI/DNA complexes internalize into cells utilizing actin-dependent pathway.
GIP, which is overexpressed in obesity, appears to bind to its G-protein coupled receptor, which signals through multiple intracellular proteins, including the cAMP and MAPK pathways
Signaling events that may increase NKCC-mediated Cl− influx include phosphorylation (star 1), protein trafficking (star 2) or decreases in intracellular Na+ (star 3)
Schematic model of regulatory pathways involved in Mycn stabilization
Glial cell line-derived neurotrophic factor can signal through activation of Src kinases in SSCs
Glial cell line-derived neurotrophic factor can signal through a Ras-induced pathway in SSCs
Schematic diagram depicting the proposed role of bone morphogenetic protein (BMP) signaling pathway, HJV, HFE, and TFR2 in iron sensing and hepcidin regulation in the liver
Schematic diagram depicting the molecular mechanisms by which inflammation activates hepcidin transcription in the liver
In glycolysis, an alternative pathway for producing ATP under mitochondrial dysfunction, two ATP, two NAD+ and two pyruvate molecules are generated for each glucose molecule consumed via a series of ten catalyzed reactions
Involvement of the Notch signaling pathway during endocrine cell differentiation
The schematic diagram demonstrates intracellular signaling events in the Ras/ERK1/2 pathway as well as the upstream and downstream cascades activated by GDNF in the C18-4 cells
PI3K is activated by binding of growth factors (GF) to a receptor tyrosine kinase (RTK) through direct interaction or adapter molecules
Molecular Biology of Renal Cell Cancer and Its Association with the Hypoxia Pathway
5-Oxo-ETE synthesis is regulated by the availability of NADP+, which is increased by oxidative stress through the glutathione redox cycle and the action of NADPH oxidase (NOX2 in phagocytic cells) and reduced by the pentose phosphate pathway, the first step of which is oxidation of glucose-6-phosphate by glucose 6-phosphate dehydrogenase (G6P-dh)
Working model of adenosine mediated intracellular signaling in corpus cavernosum
Schematic illustration of the three top ranked pathways in this study.‘Syndecan-1-mediated signaling events’ from PID; (B) ‘Signaling of hepatocyte growth factor (c-Met)’ from BioCarta; (C) ‘Growth hormone signaling pathways’ from BioCarta.
Glycolysis (blue) metabolizes glucose to acetyl coenzyme A (acetyl-CoA) in an NAD+-dependent manner
Free fatty acids (FFAs) induce hepatocyte apoptosis
Newly synthesized APP traffics through the secretory pathway to the plasma membrane, where it is primarily cleaved by the Œ±-secretase in the non-amyloidogenic pathway, producing a minimally toxic peptide P3
Extracellular signals and their signaling pathways cause posttranslational modifications of SRCs, which regulate the cellular concentrations, activities and specificities of SRCs
Axial skeleton of new born mice upon partial loss-of-function of Cdx genes and upon precocious HoxPG13 expression (A–E) and schematic representation of positive and negative regulators of axial extension before and after the trunk-tail transition (F)
GLP-1 acts by means of the GLP-1-R to stimulate adenylyl cyclase (AC), and thereby cAMP production, and to activate the cAMP-binding proteins PKA and Epac
Ligand binds to the G protein coupled receptor (GPCR) to recruit phospholipase C (PLC) which generate both diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (Ins(1,4,5)P3)
Selected IGF-axis genes that encode core components of IGF-axis upstream the PI3K/AKT/mTOR and RAS/MAPK/ERK pathway
A simplified mitogen-activated protein kinase (MAPK) pathway: complex parallel and crossover signalling cascades link the three main MAPK families, extracellular-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38, which are activated by cytokines, stress and growth factors
gp130-dependent cytokines promote axon regeneration and SOCS3 act as a critical negative regulator of the signaling pathway
The classical MAP kinase pathway is activated in human tumors by several mechanisms including the binding of ligand to receptor tyrosine kinases (RTKs), mutational activation of an RTK, by loss of the tumor suppressor NF1, or by mutations in RAS, BRAF and MEK1
Currently available therapies targeting EGFR signaling pathway
Cytokines that upregulate the MHC class I expression and assembly pathway, such as IFNs and/or TNF-α, may trigger an UPR in antigen-presenting cells of HLA-B27-expressing individuals when a critical threshold of misfolding is reached
Control of 5‚Ä≤ UTR transcript translation depends on mTOR signaling
This binding results in conformation changes of the receptor, which induces the binding of GTP to G protein Œ± subunit and the dissociation of GŒ± subunit from Gβ and Gγ subunits
Schematic Diagram of Mitochondrial Impairment Caused by Mutant Huntingtin
Estrogen pathway and cervical carcinogenesis
The cAMP/PKA signaling pathway critically regulates molecular components underlying long-term potentiation and long-term memory
Mechanisms of translation control of gene expression
Effect of estrogen on endothelium-dependent pathways of vascular relaxation
Effect of estrogen on the mechanisms of VSM contraction
Epidermal growth factor receptor (EGFR) activation, which often occurs in NSCLC, leads to upregulation of the PI3K/Akt pathway as well as the Raf/MEK/ERk kinase pathway
The model depicts several well-known aspects of the FGF signaling cascade including the synergy between FGF signaling and proteoglycans, as well as downstream effects on FGF signaling on MAPK and CDK related pathways
Hypothetical representation of regulation of calcium ion [Ca2+]i homeostasis by PKD-related proteins and summary of potential novel therapeutic interventions targeting major downstream effects of mutations disrupting this pathway
In adipocytes, overexpression of glucose-6-phosphate dehydrogenase (G6PD) increases free fatty acid (FFA) and triglyceride (TG) synthesis, decreases adiponectin and leptin synthesis, and upregulates expression of NADPH oxidases, TNFŒ± and pro-inflammatory cytokines
Current evidence suggests that Src kinases and protein kinase C (PKC) are activated in various tissues and organs in obese, hyperinsulinemic and hyperglycemic rats and mice
The Cdc34/SCF complex targets several known substrates in the pheromone response pathway
Ligation of TCR and PD-1 leads to tyrosine phosphorylation (P) of the ITIM and ITSM of PD-1
PD-1 upregulation upon TCR stimulation mediates PD-1: PD-L1 interaction between the T cell and the APC (or artificial APC consisting of epoxy bead coated with anti-CD3, anti-CD28, PD-L1-Ig and control-Ig) in the presence of TGF-β
This figure illustrates consequences of these interactions in lymphoid organs and peripheral tissues
RAD17 functions as a clamp loader for the RAD9-RAD1-HUS1 trimer
(a) Drawing of the canonical Wnt/β-catenin pathway. In the “off” state (... (b) Schematic of the noncanonical/planar cell polarity pathway. PCP migh...
In myeloid cells, chemokine mRNA instability is dependent upon AUUUA-containing ARE motifs that are recognized by TTP while in non-myeloid cells, AUUUA-free sequences produce comparable instability through undefined RNA binding protein(s)
Viruses and their antagonistic proteins are indicated at the steps of the IFN pathway they affect
Cholinergic mechanisms of modulating immune function and controlling inflammation (proposed mechanisms)
(A) EPHA2/HRAS-Erk negative feedba... (B) Positive and negative EPHB2/MA... (C) EPHA2/Akt negative feedback lo... (D) EPHA2/E-CADHERIN positive feed...
A. EPHRIN-A5 reverse signaling promotes activation of FYN, β1-integrins, and Erk in fibroblasts.
Schematic figure highlighting the complex cellular redox pathways involved in successful neonatal transitioning at birth
The VHL protein makes a complex with other proteins and targets hypoxia inducible factor for ubiquitin-mediated degradation
D2R/S100B Signaling Pathway: D2R agonist or BRC activate G-protein-coupled inhibitory receptor, D2R, causing Gi proteins to bind and inhibit adenylate cyclase cAMP production, lowering PKA activity and decreasing S776 phosphorylation of PKA substrate ataxin-1, reducing inclusion bodies and neurodegeneration
Various kinds of stress signals are detected by cells and communicated to the p53 protein and its core constituents by the mediators
p53 inhibits IGF-1/AKT and mTOR pathways thorough its induction of IGF-BP3, PTEN, TSC2, AMPK β1, Sestrin1/2 and REDD1 in response to stress
TLR 1,-2,-4, -5 and -6 are expressed in the plasma membrane where TLR2 associates with either TLR1 or TLR6
Hypothetical model for transcriptional regulation of Tspo in hormone- and cAMP- responsive MA-10 Leydig cells, and non-responsive NIH/3T3 fibroblasts
The sequential action of ecto-ATPase (CD39) and ecto-5‚Ä≤-nucleotidase (CD73), both of which can be induced by tumor hypoxia, to degrade ATP represents a primary pathway of extracellular adenosine generation in the tumor microenvironment
Activation of the β 2AR with isoproterenol increases cAMP which then activates PKA
(a) PI3K pathway regulates trafficking and PSD-95 to a synapse and cAMP regulates formation of synaptic PSD-95-TrkB complex
Three pathways lead to activation of complement
Putrescine (diamine), spermidine (triamine) and spermine (tetramine) are the major polyamines
A. Anaphylatoxins are produced and act locally within the immunological synapses.
Putative model for the intracellular signaling pathways involved in NPY-induced VSMC proliferation
Chemical structures of NAD+, PAR, and metabolites
Model for GnRH receptor (GnRHR) signaling within the pituitary gonadotrope that leads to LH biosynthesis
A GeneGO pathway map is shown to illustrate the interactions between the selected proteins
(a) An intricate network of soluble and cell-surface- bound proteins ena... (b) On healthy human cells, any complement activation or amplification i...
Quercetin induces c-fos gene expression through upstream activation of p38 and CREB and potentiates the response to UVB, leading to an increase in steady state c-fos mRNA levels
A reconstructed antioxidant regulation pathway of detoxifying proteins
Reproduced with kind permission from PharmGKB and Stanford University []
Relationship of P.gingivalis Infection and AtherosclerosisAs the bacterial load of P.gingivalis in the oral cavity increases periodontal disease becomes more severe
Lung cancer cells predominantly express ERβ
The 447 TFAP2C target genes were analyzed using Ingenuity Systems to determine associations between genes for the purpose of defining physiologic pathways regulated by TFAP2C
Leptin-induced upregulation of VEGF expression in MT mainly involves the activation of HIF-1Œ± and NFŒ∫B through leptin canonic (PI-3K/AKT1 and MAPK/ERK1) and non-canonic (JNK, p38 and to less extent PKC) signalling pathways
The VHL E3 ubiquitin ligase complex targets the hypoxia inducible factors for ubiquitin-mediated degradation
The VHL complex targets HIF-1α and HIF-2α for ubiquitin mediated degradation
A. FLCN is the gene for the Birt-Hogg-Dubé (BHD) syndrome.
A grey shaded molecule refers to a probe that was more abundant in acute KD subjects vs. both convalescent KD subjects and healthy control as well as more abundant in IVIG-resistant compared to IVIG-responsive KD subjects.
Inflammatory signaling pathways activate indoleamine 2,3-dioxygenase (IDO) which converts tryptophan to the neuroactive metabolite intermediary kynurenine
Synthesis of PAF by the remodeling pathway
Schematic illustrating putative molecular pathways mediating the effects of centrally administered LPS on sympathetic drive
NQO1 catalyzes the obligatory 2-electron reduction of estrogen quinones to catechol estrogens which can then be conjugated and excreted
The major transcription factors involved in the promyelinating to myelinating transition are depicted with their regulatory relationship
Being coupled to stimulatory (Gs/olf) and inhibitory (Gi/o) GTP-binding proteins, D1 and D2 receptors have opposite effects on the adenylyl cyclase/cAMP/PKA/DARPP-32 cascade (‘canonical pathway’), which regulates the levels of phosphorylation of multiple cellular and nuclear targets
Potential signal transduction mechanisms involved in the mediation of cellular responses induced by secreted MIC-1 cytokine in certain cancer cells
Targeting of signaling pathways by arsenic trioxide in chronic lymphocytic leukemia cells
A model depicting a novel mechanism by which cetuximab induces autophagy
A hypothetical model of how Str1 may affect cellular behavior via the β-catenin/LEF signal transduction pathway
Activin signaling regulates transcription of the FSHβ gene
LTβR signaling regulates mTECs development and function in various ways
Implications of PC12 cell microarray/transcriptome analysis for pituitary adenylate cyclase-activating polypeptide (PACAP) actions, and PACAP-activated signaling pathways, in vivo
Hypothetical model for SUMO regulation in NFŒ∫B pathway
Rapid growth of early melanoma tumor nodules causes them to outgrow their blood supply and creates hypoxia
The established pathway of Rho signaling is through ROCK and LIM Kinase to inactivate cofilin, an actin-severing protein
Shown are the two major insulin signaling pathways
Leptin, IGFBP3, and rapamycin suppress the IGF-1 signaling pathway to preserve naïve T cells and promote longevity
The CD28 signaling pathway in T cells is equivalent to the IGF-1 pathway in the whole organism
Reactive oxygen species, UV light or other genotoxic stresses, that induce DNA damage, principally, double-stranded breaks, is detected by the MRE11-RAD50-NBS1 complex, which in turn activates ATM
E2/ERβ-mediated signaling pathways and Interaction with BRCA1; 2) E2/GRCP-30/EGFR signaling pathway; 3) CXCL8 and related CXC Chemokines; 4) MicroRNA signatures; 5) Notch/Suvivin; 6) Akt; 7) E-cadherin/E-Selectin and 8) Osteoponin are shown
At a basal level, NIK undergoes constant proteosomal degradation, executed by four E3 uibiquitin ligases, cIAP1/2 and TRAF2/3
The diagram depicts a summary of the data obtained in this study
Phosphoinositide signaling cycle, showing the generation of second messengers and the resynthesis of phosphatidylinositide substrates
Schematic of dopamine-sensitive signaling via adenylyl cyclase (AC), phospholipase C (PLC), and phosphatidylinositol-3-kinase (PI3K) systems
LOV inhibits HMG-CoA reductase of the mevalonate-pathway resulting in the depletion of cholesterol and isoprenoids i.e., farnesyl-pp and geranylgeranyl-pp responsible for an inhibition of Ras and RhoA signaling, respectively.
Host anti-viral signals are initiated when cells sense the presence of pathogens via pattern-recognition receptors (PRRs) such as extracellular toll like receptors (TLRs), or intracellular RIG-I like helicases (RLHs) or DNA binding proteins
PTEN is the lipid phosphatase that negatively regulates the PI3K signaling pathway
The PTEN regulated PI3K/AKT signaling cross talks with several other signaling pathways
H2AX is phosphorylated by members of the phosphatidylinositol-3 kinase (PI3K) family; which one is involved depends on the type of genotoxic stress ()
Membrane-bound wild type EGFR is activated after binding its ligands: epidermal growth factor (EGF) or transforming growth factor-α (TGF-α)
The mechanisms by which paraquat enters the cell are still unknown
In the protective model of live-attenuated sporozoite vaccines [irradiated sporozoites (irrSPZs) or genetically attenuated parasites (GAPs)], elimination of pre-erythrocytic-stage parasites is primarily dependent on antigen-specific and major histocompatability complex (MHC)-restricted CD8+ T cells, whereas recombinant vaccines, such as the CSP-based RTS,S vaccine, are primarily dependent on CD4+ T cells
A schematic of the drug- and cytokine-induced hepatocellular death signaling network, curated from literature references-, -
Death receptor signaling and its interdigitation with the mitochondrial pathway of apoptosis
The signaling core of the Tor pathway integrates the activity of growth factor signaling like insulin and wnt, hypoxia, energy stress and amino acid sufficiency to regulate translation initiation
The Calcium Signaling Pathway (KEGG, Kanehisa Laboratory in Kyoto University, Japan) with vinclozolin altered genes indicated
Gene interaction sub-network of shortest connections to common targets for the 36 candidate regulatory genes obtained by global literature analysis (Pathway Studio 7.0, Ariadne Genomics Inc., Rockville MD)
Members of the RB pathway that are expressed in hESCs are shown
Emerging evidence suggests that members of the RB pathway are regulated by and function with factors involved in the maintenance of self-renewal and stemness in hESCs
A schematic drawing of proposed underlying mechanisms of the bee venom (BV)-induced chemically relevant persistent nociception (CRPN) in the spinal cord dorsal horn
Proposed mechanism of the regulation of cell migration and invasion by PTHrP, involving activation of Rac1
The mutant epidermal growth factor receptor, EGFRvIII, promotes cell survival and proliferation by preferential signaling through the phosphotidyinositol-3-kinase (PI3K) pathway
A working model of merlin-mediated signaling events and their potential cross-talks (the components of Drosophila Hippo signaling pathway are underlined): merlin functions upstream of the mammalian Hippo (merlin-MST1/2-LATS1/2-YAP) and JNK/p38 signaling pathways and plays an essential role in regulating the cell response to the stresses and stress-induced apoptosis as well as to proliferation/survival signals
(A) Transforming growth factor beta (TGF-β) family cell signaling pathwa... (B) Receptors and Smad proteins that comprise the core signaling pathway...
A. Opposing effects of synaptic vs. extrasynaptic NMDAR signalling on CREB-dependent gene expression.
A) Synaptic NMDAR signalling suppresses the intrinsic apoptosis cascade at multiple levels
(A) In response to DNA damage Eukaryotic cells activate a complex signal... (B) Detailed knowledge of DNA damage induced signaling pathways has grea...
Diagrams of relationships of selected proposed interactions between signaling pathways that influence proliferation and differentiation
Proposed model of IL-1 signaling in prostate
Microarray data from luteolin-treated PC-3 cells (17.5 µM for 6 hours) relative to controls described in detail in Shoulars et al, J Steroid Biochem Mol Biol,118: 41–50, 2010 were analyzed with Ingenuity Analysis Software.
Insulin, IGF-I and IGF-II signaling through the IGF-IR
The HBP combines various metabolic inputs to ultimately serve in the synthesis of UDP-GlcNAc, the donor substrate for OGT
During prolonged insulin signaling O-GlcNAcylation of key molecules have an affect on the attenuation of the insulin signaling cascade
Proposed model of Dkk3 and Krm in regulating Wnt signaling
Shown are the signaling pathways that regulate the pioneer round of translation (top) and subsequent steady-state translation (bottom)
Summary schematic illustrating the adaptations of select genes of the IGF-1/PI3K/Akt pathway involved in protein synthesis and degradation analyzed in the plantaris muscle
Glucose-derived carbon can be converted by SCOT into acetoacetate that is exported from the mitochondria to the cytosol and, ultimately, converted into short chain acyl-CoAs in the cytosol (thick arrows)
In the canonical pathway, binding between transmembrane Notch receptors and its ligands triggers ADAM10- and Presenilin-mediated proteolytic cleavage
JS genes implicated in the Shh, Wnt, and PDGFŒ± signaling pathway
Oligomeric Aβ intermediates increase intacellular Ca2+ levels, possibly through cell membrane destabilization ()
Simplified scheme of the double-edged role of Akt in tumor development
Hypothetical model for SWAP-70 function in mast cell FcŒµRI signaling
Schematic illustration of potential mechanisms by which SHP-1 regulates mast cell development and function
A proposed signaling pathway by which the mutant GPD1-L and NADH downregulate cardiac Na+ channel by causing PKC activation and ROS overproduction from the complex III of mitochondrial electron transport chain
All three pathways converge at the third component of complement (C3) which is activated by pathway-specific C3 convertases []
P. gingivalis is recognized by the CD14/TLR2/TLR1 receptor complex [].
Both receptors and ligands contain multiple conserved domains
This figure shows the two distinct but ultimately converging apoptosis signaling pathways in mammals
This figure shows the mechanisms that control FASL-FAS induced apoptosis and BIM-dependent ‘BCL-2-regulated’ apoptosis in activated T and B cells during shutdown of acute or chronic immune responses.During shutdown of an acute T cell immune response (left side, top panel), the reduction in the concentrations of cytokines, such as IL-2 and IL-7, leads to a reduction in PI3K and AKT
This figure shows the two distinct modes of caspase-8 activation – the well-known ‘death receptor’ apoptotic pathway involving caspase-8 auto-processing (shown on the left) followed by either direct activation of effector caspases or proteolytc activation of the BH3-only protein BID to activate the ‘BCL-2-regulated’ apoptotic pathway (see also )
Model of crosstalk between mAchR and VEGFR2 signaling
Repairing toxic DNA lesions induced during most common cancer treatments relies on proper DNA-repair response, which has the ability to dictate the cellular outcome, e.g.
Schematic diagram showing the interaction of the p75NTR and TrkB signaling pathways
a | Membrane-bound β-catenin links cadherin receptors to the actin cytoskeleton, and in non-transformed epithelial cells β-catenin is primarily localized to E-cadherin complexes
Genes in one pathway have complex “net” interactions, which should be taken into consideration when analyzing proteomics/genomic data
(A) Simplified diagram of afferent/efferent connections of, and internal... (B) Comparison of CA1 microcircuits in wildtype and ErbB4−/− mice. nNOS...
Synaptic long term potentiation canonical pathway in adolescent rats treated with chronic nicotine
Working model of IR activation in rod photoreceptor cells
The calcineurin–NFAT (nuclear factor of activated T-cells) pathway and its possible regulation by vasoactive intestinal peptide (VIP)
Normal biology of the VHL-HIF axis in the setting of (A) normoxia and (B) hypoxia
Binding of the HIFα–HIFβ heterodimer to the HRE in the promoter region results in transcriptional upregulation of genes important to the cell’s response to hypoxia
Current data indicates thatTGF-β1 activates two distinct signaling pathways that initiate transcription of PAI-1
This schematic shows links between the PAR-3/PAR-6/aPKC polarity proteins and a variety of other signaling networks
(a) Understanding the basis for modular connect... (b) Circuit diagram representation of the model... (c) The MAP kinase pathway that mediates mating...
‘Selecting’ DP thymocytes and iNKT ‘precursor’ cells communicate via invariant TCR-CD1d and SLAM family (SLAM, Ly108) interactions
(a) The complement cascade after activation by pathogens. In addition to... (b) Regulation, deactivation and inhibition of the complement cascade on...
Schematic diagram of mechanisms involved in alcohol-mediated suppression of type I IFN pathway in human hepatocytes
The amino acid sequences of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are given, demonstrating the high degree of homology shared by the peptides
These signaling pathways include the dominant growth hormone secretagogue-related PLC/PKC/IP3 pathway, hypothalamic ghrelin activation of NPY-containing neurons and inhibition of POMC neurons, and ghrelin augmentation of dopamine signaling, involving GHS-R1a/D1R heterodimerization, leading to a synergistic activation of AC2 via GŒ±s (D1Rcoupling) and βγ-subunits derived from GŒ±i (GHS-R1a coupling)
Variant: non-synonymous coding SNP rs4880 of SOD2 gene, T (Valine) ‚û° C (Alanine)Function: C variant associated with better mitochondrial targetingHypothesis: C variant associated with less toxicity but poorer survival after treatment
(A) Non-linear relationship between total paxillin and cell tension, summarizing the various findings
SLIT can inhibit invasion and promote a cell cycle arrest by blocking Wnt, HGF and SDF-1 signalling
The “canonical pathway” (center) is stimulated when Wnts bind to Fzd receptors and Lrp5/6 co-receptors
Growth factors acting through these pathways are indicated
TNF-dependent signalling pathways mediated through TNFR1 and TNFR2
Ca2+ waves activate transcription factor NFAT that in turn controls cell cycle
Intracellular signaling pathway within cranial neural crest cells mediated by endothelin-1 (Edn1)
The Oxidative Stress—Chronic Stress Cycle of Aging
The 19 Wnt ligands are recognized by cell surface receptors (Frizzled, LRP5/6, and ROR2)
Schematic representation of the molecular mechanisms of estrogen receptors
The classical and non-canonical NF-Œ∫B pathways
Those proteins identified in this work by two ore more peptides are shaded in grey
Cytokines, hormones or growth factors that activate Stat5
Model demonstrating the specific apoptotic effect of SREBP-1 and FAS inhibition on GBM cells bearing EGFRvIII
Double strand DNA repair: Homologous recombination and Non-homologous end joining
Control of the HiNF-P/p220NPATpathway by p57KIP2
Two signalling pathways downstream of mGluR5 affect translation the MEK-ERK-Mnk1 and the PI3K-mTOR pathway
Wnt signaling is broadly divided into ß-catenin-dependent and ß-catenin-independent pathways
The signaling pathway mobilized by GPIbŒ± in response to botrocetin (bt)/ von Willebrand factor (VWF) treatment of suspension washed mouse platelets
Model of deoxycholyltaurine-induced post-EGFR signaling in human colon cancer cells
The intrinsic pathway can be initiated by the release of proapototic molecules such as cytochrome c, from damaged mitochondria, which activate the intracellular receptor Apaf-1 (Apoptotic Protease-Activating Factor 1) forming with caspase-9 a proteotically active structure called the apoptosome []
Oxidative stress-inducing agents directly activate the NSMase-ceramide pathway
Activity reduction of Dmp53 in the Drosophila insulin-producing cells leads to down regulation of dILP2 abundance by unknown mechanisms
(A) Rapid association of Ku to DSB... (B) Alternatively to NHEJ, MRN, wh... (C) Limited DSB resection carried... (D) Following DSB resection, 3′-ss...
Proposed model highlighting UPR (unfolded protein response) pathway with pro-apoptotic and anti-apoptotic protein signatures triggered by ER stress in alcohol treated monocyte derived dendritic cell
A. Pathways in cell lines with and without constitutive pAKT expression.
Canonical pathways for cardiovascular disease
CFTR, NHERF1, and β2AR form a macromolecular complex together with signaling molecules at the apical surfaces of airway epithelia
LPA2 and CFTR are physically associated with NHERF2, which clusters LPA2 and CFTR into a macromolecular signaling complex at the apical plasma membranes of gut epithelia
Activation of Foxos in response to oxidative stress is mediated by reactive oxygen species (ROS)-activated kinases, such as JUN N-terminal kinase (JNK) and by the ROS-induced interaction of β-catenin with Foxos
In addition to conventional cell cycle regulatory target genes, E2fs have been reported to interact functionally with other transcription factors, such as Foxos, hypoxia-inducible factor 1α (HIF-1α), nuclear factor κB (NFκB), nuclear respiratory factor 1 (NRF1) and peroxisome proliferator-activated receptor γ (PPARγ), to modulate effects on autophagy, metabolism, mitochondrial mass and the redox response of cells
Functional network identified by genes in the single nucleotide polymorphism (SNP) component using independent component analysis
Signal-transduction pathway of iloprost-stimulated vasodilation resulting from RBC-derived ATP release and endothelium-derived NO production
Retinoids absorbed from food are converted to retinol and bound to CRBP in the intestine
FC-66 expression of the Ingenuity NF-Œ∫B Signaling canonical pathway
Our data suggests that age associated MMP-1 expression is redox-sensitive
A simplified network for the canonical NF-Œ∫B pathway consisting of active IKK, IŒ∫BŒ±, and NF-Œ∫B are represented in a navigational map (A) and in a schematic diagram (B)
Genes associated with autoimmunity regulate the CD40/NF-Œ∫B signaling pathway
Model for negative regulation of junctional stability in RPE by the PI3K–ROS circuit
Genomic and non-genomic responses of vitamin D receptor binding to 1,25(OH)2D.In the genomic response, 1,25(OH)2D binds to the nuclear vitamin D receptor (VDR)
(A) Autophagy and caspases may function in a parallel genetic pathway, a... (B) Autophagy and caspases may function in a common regulatory hierarchy...
Proposed mechanism of carnosol in human prostate cancer PC3 cell line
Simplified MAPK signaling pathway diagram depicting places where Mn has (demonstrated previously and in this study) an effect
Immune and central nervous systems interact and contribute to the etiology and pathophysiology of cytokine-induced depression
Prorenin and renin effects via PRR include Ang II-dependent and independent actions
Proposed model of GF-mediated regulation of IGFBP-3
Mechanisms of autoinflammatory disease regulated by IL-1β (inflammasomopathies) and NF-Œ∫B
Model illustrating the signaling pathways activated by optimal DA and hyperdopamine
Novel therapeutic strategies against aggressive and recurrent epithelial cancers by molecular targeting distinct signaling pathways and multidrug resistance-associated molecules involved in aggressive behavior and resistance phenotype of tumorigenic and migrating cancer stem/progenitor cells
They result in aberrant activation of non-canonical and canonical NF-Œ∫B pathway that together with other signaling pathway activation (JAK/STAT, MAPkinase, PI3K/AKT) trigger myeloma cell survival, proliferation and drug resistance
Chromatin modification upon growth factor stimulation and the effect of small molecule inhibitors
Screen shot of the user interfaceofSimmune2.0
Model Depicting major molecules and events in mast cell activation
Schematic representation of decorin effects as an antiproliferative (left panel) and proliferative (right panel) molecule
. A signaling scheme describing the relationship between laminar flow-mediated ERK5/MEF2/KLF2/eNOS pathway and H2O2 or AGE-mediated ERK5-SUMOylation.
NOD1 and NOD2 recognize peptidoglycan fragments released either during bacterial division within the cytosol or by the lysosome during the degradation of phagocytosed bacteria
Schematic showing the positive control of cardiac function through classic β-adrenergic pathway and a negative control of cardiac function through the Œ±-adrenergic pathway
MHC class II antigen processing pathways containing P
Toll-like receptor signaling pathways containing P
Both pathways are dependent upon a SFK, possibly Src
GDP-fucose can be synthesized in the cytoplasm from GDP-mannose (de novo pathway) or from free fucose (salvage pathway)
(A) In the presence of oxygen (O2), PHDs hydroxylate proline residues of... (B) The role of hypoxia responsive genes in different steps of metastasis.
The major nuclei of the basal ganglia are shown and the localization of various mGluR subtypes that are relevant to PD therapeutics is highlighted
A) Transcriptional silencing of c-Myc by Smad complexes is a core event... B) TGFβ induces expression and nuclear accumulation of NFAT, which binds...
THC induces apoptosis in Jurkat cells via three different mechanisms
EGFR forms a homodimer after ligand activation, which results in phosphorylation/activation of the intra-cellular kinase domain and a cascade of downstream signaling including activation of the Ras/Raf/MAPK and phosphoinositol-3-kinase (PI3K) pathways that are associated with cell growth, differentiation, survival, and invasion
Ingenuity pathway analysis of genes deregulated as a consequence of silencing RRM2 (A and B), RPS2 (C and D), and NOL5A (E and F)
Cellular and molecular scheme for an adaptive immune axis leading to acute lung disease after viral infection
Schematic of the signaling cascade from PLD to HDM2
The double ovals in dark grey and the light grey ovals represent generic dimerized cell-surface receptors binding to their ligand
Cell adhesion (immune system) molecules pathway containing Treponema denticola differentially regulated genes in calvarial bone (A) and tissue (B) compared with sham-infected controls at P ‚â§ 0.05, adapted from Pathway Express and using the Kyoto Encyclopedia of Genes and Genomes nomenclature.
Cell cycle pathway containing Treponema denticola differentially regulated genes in calvarial bone compared with sham-infected controls at P ‚â§ 0.05, adapted from Pathway Express and using the Kyoto Encyclopedia of Genes and Genomes nomenclature
Cell Cycle pathway containing Treponema denticola differentially regulated genes in calvarial soft tissue compared with sham-infected controls at P ‚â§ 0.05, adapted from Pathway Express and using the Kyoto Encyclopedia of Genes and Genomes nomenclature
The phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway becomes activated via stimulation of receptor tyrosine kinases (RTKs) and the assembly of receptor–PI3K complexes
RAS, an intracellular G protein, is phosphorylated, leading to activation of RAF (depicted as BRAF)
Sites of action for inhibitors and shRNAs in the EGFR-PI3K-Akt-mTOR pathway
Regulation of glucose-dependent insulin secretion in the β-cell
Recently, additional classes of pro-resolution mediators derived from DHA have also been identified in resolving inflammatory exudates that display protective bioactivities, namely protectins and maresins (named for macrophage mediators in resolving inflammation) [,]
Biosynthetic pathway of sphingolipids that mediate expressions of genes associated with cellular processes in cancer
TLR4 activates ERK pathway via IKKβ-mediated phosphorylation of p105
Schematic illustration of the interaction between cPLA2Œ± and TGF-βsignaling pathways in hepatic cells
a) An upregulation of AKAP-Lbc facilitates PKD... b) Calcium mediated activation of AKAP150-targe... c) mAKAP organizes ubiquitin E3 ligases that ma...
Model of the PPARγ signaling pathway in human macrophages in response to virulent M
In human primary macrophages, zymosan activates a calcium-dependent CaMKII–Pyk2–ERK signaling pathway downstream of Dectin-1 and ITAM-associated kinases Src and Syk
Schematic representation of the p38MAPKsignalling pathway
Schematic illustartion of microglial (A) and astrocytic (B) events taking place in the spinal cord in neuropathic pain
In haploid yeast cells, mating is initiated by the binding of pheromone to a G protein-coupled receptor
In the ‘classic’ pathway, pheromone binding to a cognate seven-transmembrane receptor leads to the activation of the Gα subunit of a receptor-coupled heterotrimeric G-protein
Schematic cartoon of selected elements of the yeast mating pheromone response pathway (see text for details)
Wiring diagram of selected elements of the yeast mating pheromone response pathway (see text for details)
FcεRI aggregation by cell surface-bound IgE antibody interaction with a multivalent antigen leads to the phosphorylation of the receptors β- and γ-chain immunoreceptor tyrosine-based activation motifs (ITAMs) by Lyn kinase
A composite figure from all time points of microarray data showing apoptotic pathways in HepG2 cells when exposed to PCB-153 (70ŒºM) and PCB-77 (70ŒºM)
The main function of membrane-attached GPC5 is thought to regulate the pathway signaling of Wnt, Hedgehogs (Hh), and fibroblast growth factors (FGFs)
Functional significance of itpkc_3 on ITPKC mRNA and Ca2+/NFAT pathway
A, the ability of a MEK to interact with its cognate MAPK both by an active site-target residue interaction (1) and by a docking interaction (2) comprises, in principle, a “double selection” that has the potential to promote the efficiency and fidelity of MAPK activation
(A) Prior to replication we propose that SP sites in Mcm4 and Mcm6 are phosphorylated either by G1-CDKs or Pho85
Current working model of convergent pathways to PMF
Ginsenoside Rh2 induces both apoptosis and paraptosis in colorectal cancer cells
Alcohol-induced TLR4 protein recruitment mediates the activation of Src kinase signaling pathway
Physiological regulation of the mTOR signaling pathway
A) The “canonical pathway” is stimulated when W... B) Secreted frizzled-related proteins (Sfrps) a... C) Dickkoph (Dkk1) suppresses Wnt signaling by...
PLA2 may mediate excitotoxicity, cerebrovascular dysfunction and oxidative stress in AD
Cell positioning and signaling compensate for stochastic lateral inhibition in the worm vulval developmental pathway
Both PROG and VDH are pleiotropic and affect multiple pathways, which may account for their therapeutic effectiveness
Receptor tyrosine kinases (RTKs) are transmembrane proteins that dimerize when bound to ligand
A. Pathogens: Figure depicts age-associated changes in signaling mechanisms leading to increased cytokine secretion in response to pathogens and decreased phagocytosis and migration of DCs.
Working model of cellular mechanisms giving rise to pLTF
Molecular mechanisms activated by tumor necrosis factor-alpha (TNF-Œ±) which causes hypercontractility of cavernosal smooth muscle cells
The mTORC1 and mTORC2 signaling branches
The paracellular pathway in vertebrates and insects
(a) In unstimulated T cells, CARD11 is kept in... (b) Upon TCR engagement, PKCŒ∏ clusters at the... (c) Subsequent to the activation of CARD11, GAK...
The canonical pathway is activated by cytokines such as TNF-Œ±
Adapted from KEGG colorectal cancer pathway [, , ]
Activation of the β2AR with isoproterenol increases cAMP with subsequent PKA activation
The evidence used to generate this figure is discussed in [section III.B.].
Thrombin activates both PAR1 and PAR4 following vascular injury
Regulatory network governing mitochondrial functions orchestrated by PGC-1Œ±
Osteoblast differentiation is induced by several receptors, and leads to the activation of osteoblast transcription factors, including runt-related transcription factor 2 (Runx2), osterix, and Dlx5
Shown above are all members of the MAPK pathway as recorded in KEGG ()
Pathway analysis of gene expression profile
Simplified model of nutrient signaling pathways influencing metabolic responses
Interaction between PI3K/Akt and Wnt signaling pathways mediates diverse cellular effects through downstream messengers
The p160 ROCK is activated by several upstream pathways, including activated Rho-GTP and activated caspase 3
Mutations in non-essential genes affecting stress response pathways confer Ino‚àí phenotypes
Major pathways of lipid metabolism in yeast
Mechanisms of activation of the PI3K/Akt pathway in cancer
Heterodimers of HER2/ErbB-2 and either EGFR/ErbB-1 or the kinase-defective ErbB-3/HER3 (note the letter X that symbolizes a defective cytoplasm-facing kinase domain) are shown, along with the growth factor ligands they bind
Jnk, a stress activated protein kinase, is activated by diverse stimuli, including caspase activation, ligands for Jnk signaling pathways (Egr), cellular stresses (reactive oxygen species, infection, cytoskeletal changes), and loss of apical-basal polarity (; )
PI3K/Akt and RAS/BRaf/MEK pathways are frequently altered in melanoma
Strategies to increase flux of non-natural analogs into glycosylation pathways
The PD-L1 promoter has binding sites for transcription factors IRF-1 and NF-κB, so IFN-γ-mediated signaling through the JAK/STAT-1/IRF-1 pathway and TLR ligand-mediated signaling through the MEK/ERK/NF-κB pathway can upregulate PD-L1 gene transcription
APCs (light blue) take up antigens (red circles) released from tumor cells and present them to T cells (pink) in the context of B7-1 and B7-2 costimulation
Shown are the changes in the signaling pathways during the first 24 hours of blast colony development
Proteins oxidized by extracellular EhCySS control cell signaling and morphology
For this model our gene list was restricted to the 28 most significant proteins, as determined by their presence on at least two of the five gels, and to the top 50 genes (p<.00045) from the cDNA microarray analysis.
TLR4 and TLR2 activate the transcription factor XBP1 by selectively activating the IRE1 kinase while suppressing the other branches of the ER-stress pathway
Signaling pathways regulating dendritic spine actin remodeling with the induction of LTP by theta burst stimulation (TBS).Schematic of signaling pathways linking three classes of synaptic to regulation of the actin cytoskeleton
IFNŒ±/β and IFNγ activate parallel signaling pathways
Bending or activation of the cilia involves mechanosensory polycystin-1 and polycystin-2 complex, which results in biochemical synthesis of NO
Bending or activation of the cilia results in maintaining cytosolic calcium (Ca2+), followed by activation of inversin
Under normal conditions, the carboxy terminal tails of polycystin-1 and polycystin-2 interact, which enables calcium entry into the cell
In healthy kidney cells, the cysto-protein complex interacts with tuberin
TNF-Œ± is shown as a representative inducer of the canonical pathway
Red dashed lines represent known inhibition of target enzymes with methotrexate
Enzymes involved in the synthesis of fumiquinazoline intermediates 14 and 18
Pmar1 de-repression system initiates the entire PMC specification program, and activates Alx1, Ets1 and other PMC regulatory genes (light blue oval), which in turn regulate skeletogenic differentiation genes (dark blue box)
This representation of the hypotheses presented in the text helps explain cellular innate responses to CVB infection
Memory genes identified in model systems overlap with genes identified in human mental retardation
Learning and short-term memory depend on the cAMP pathway
Overview of the molecular mechanisms involved in nasopharyngeal carcinoma (NPC) development
Architecture of intestinal TD and TI IgA responses
TGFβ Smad-dependent signaling pathway: TGFβ exerts its effect by binding and activating type II receptor (TGFβR2) and then type I receptor (TGFβR1)
TGFβ Smad-independent Signaling Pathways: TGFβ exerts its effect by binding and activating type II receptor (TGFβR2) and then type I receptor (TGFβR1)
Ingenuity Pathways Analysis of the differentially expressed genes in the MICs as compared to NSPCs
FSS promotes the vesicular release of ATP, where it binds to metabotropic P2Y or ionotropic P2X receptors; activation of P2X7 causes ERK1/2 phosphorylation, although this is not involved in IŒ∫BŒ± degradation, and nuclear localization of NF-Œ∫B
Schematic representation of Wnt signaling pathway activation in R1Œ± deficient tumor cells
Multifunctional effects of CMKLR1 activation
Pathway Studio 6 was used to construct a pathway from all phosphoproteins that had a higher signal in ŒîEGFR vs ŒîEGFR-ki and a p<0.05 in statistical analysis (red).
Diagram of the major kinase signaling cascades involved in drug addiction
TGF-β normally suppresses cell proliferation and induces cell apoptosis through the activation of the pSmad3C mediated p21 WAF1pathway and down regulation of anti-apoptotic proteins
There are two cell death checkpoints in the TNFR1 pathway
Subtype-specific G protein coupling and function of β1 AR and β2 AR in cardiac myocytes
A proposed model explaining upregulation of CREB expression by RA in NHTBE cells
Hh pathway is silent in Hh-responsive cells when Hh ligands are absent
At left, the pathogenic autoantibody pathway can involve autoantigens, which in health are primarily sequestered in the nucleus
Ligands with different efficacies (inset) can modulate a given signaling pathway
Several mechanisms have been proposed by which PrPC to PrPSc conversion results in neurodegeneration
The role of impaired brain insulin signaling in sporadic Alzheimer’s disease (sAD) pathology
(A) Toll-like receptors (TLRs) signal through the adaptor molecule myelo... (B) The ligation of Fcγ receptors signals through a different protein ki...
Attachment and entry of infectious virus–antibody complexes into Fc receptor-bearing cells results in increased production of virus by inhibition of type I interferon and production of proinflammatory cytokines
Exploiting the synthetic lethal relationship between PArP1 and BrCA1/2 for the targeted treatment of HR-deficient human tumors
Exploiting synthetic lethal interactions for the treatment of human cancer
I. Phase I (initiation): mTOR (mammalian target of rapamycin)-dependent and mTOR-independent pathways can induce autophagy.
Various intra- and extracellular environmental cues activate the TOR signaling pathway leading to modulation of various biological processes that can modulate lifespan of flies
Schematic diagram showing the RAS-MAPK cascade and affected disease genes in disorders of the neuro-cardio-facial-cutaneous syndrome family
A metabolic scheme depicting the involvement of different types of PLA2s in oxidative signaling pathways leading to neuronal impairment and glial cell inflammatory responses
Antiviral apoptotic pathway is mediated by IRF-3 and Bax
Schematic representation of SP-mediated signaling and activation of the MAPK and MLC20 pathways in lymphatic muscle cells
A. VEGF in the circulation binds to VEGFR-2 expressed on endothelial cells, triggering the production of NO by activation of eNOS.
Pathway network modeling of statistically enriched local networks involved in the re-activation of p53 in Capan-2 cells post 32 hr treatment as described in
[A & B] Pathway network modeling of MI-219 treated at 16 and 32 hrs showing down-regulation of HNF4α and related network genes; [C] Pathway network modeling of combination treatment showing down-regulation of HNF4α target genes
TSC mediated signaling in the central nervous system
Biogen-Idec has developed mouse monoclonal antibodies (mAbs) that bind to the NH2-terminal region, EGF-like domain or CFC motif of Cripto-1
ESCs are characterized by hyperdynamic chromatin, which is compacted when these cells exit from their pluripotent state and differentiate into cells of multiple lineages
Death receptor mediate death ligand-induced apoptosis through the formation of a death inducing signaling complex (DISC) containing the death receptor, adapter proteins such as Fas-associated death domain (FADD), and initiator caspases such as pro-caspase-8 or pro-caspase-10
The oral administration of 5-ALA (20 mg/kg) leads to a selective accumulation of PPIX in tumor cells as well as epithelial tissues
Model of the bifurcating parallel signal transduction pathways downstream of the IL-13R that regulate 15-LO gene expression in primary human monocytes
Two different ubiquitin ligases control the stability of the Aurora-A and Polo-like kinases
The major signaling pathways stimulated by receptor tyrosine kinases (RTKs) and TGF-β receptors are shown schematically
A scheme showing the major therapeutic strategies aimed at blocking growth factor signaling in cancer
Proposed mechanisms of IL-6 and its receptor signaling pathway in SOCS-3 induction in cells with or without IL-6R
a | While capturing antigen, intestinal dendritic cells (DCs) are exposed to microbial Toll-like receptor (TLR) ligands and epithelial-cell-derived cytokines, including thymic stromal lymphopoietin (TSLP)
Metabolic insulin signaling pathway genes genotyped in the discovery cohort
In response to ligand stimulation, GPCR signaling can occur via both G-protein mediated pathway (which leads to activation of second messengers) or via β-arrestin mediated pathway which further stimulate a plethora of downstream signaling pathways (MAPK, PI3K, AKT, EGFR etc.)
Effects of dietary agents on the extrinsic and intrinsic pathways of apoptosis in prostate cancer
Interconnectivity of signaling pathways emanating from TLRs and TACI
Analogue 3 also showed potent antiproliferative activity against the highly invasive non-small-cell lung cancer cell line CL1-5 with an ED50 value of 0.11 ŒºM
Defects in nucleotide excision repair (NER) lead to at least three human syndromes characterized by neurodegeneration and DNA repair; xeroderma pigmentosum, Cockayne syndrome and Trichothiodystrophy (also see )
Schematic representation of the evolutionarily conserved Wnt/Wingless signal transduction pathway
Simplified schematic representation of the apoptosis pathway in mammals and Drosophila
Significantly expressed genes in cytokine–cytokine receptor interaction pathway disturbed by SM at different time points
Divergent evolutionary pathways of breast cancer progression
Through a putative GPCR (mER), E2 (and STX) activates a PLCβ-PKCŒ¥-AC-PKA pathway in POMC neurons that attenuates the coupling of Œº-opioid and GABAB receptors to GIRK channels (heterologous desensitization) and triggers the release of Ca2+ from intracellular stores
A. After exposure of young animals (3–4 weeks of age) to an enriched environment for 2 weeks a new LTP inducing signaling pathway appears that involves NMDA type glutamate receptor activation of p38 MAP kinase potentiated by cAMP.
The cRGD-induced apoptosis hypothetical pathway
(a) Some iNKT cell hybridom... (b) A combination of pro-in... (c) Upregulation of co-stim... (d) Under certain condition... (e) Following activation, h...
Representative axon regeneration-regulating pathways discovered in genetic model organisms
TNFŒ±, released from macrophages or microglial cells, stimulates the p38 mitogen-activated protein kinase (p38 MAPK) pathway to increase phosphorylation (P) of cAMP response element (CRE)-binding (CREB), a transcription factor known to regulate the BDNF gene
Stimulation of receptor tyrosine kinases (RTKs) by growth factors activates the Ras-Raf-MEK-ERK pathway and leads to the accumulation of phosphorylated active ERK1/2 in the nucleus
The top-scoring network created by Ingenuity Pathway Analysis
Pro-B cell development is supported by IL-7 stimulation via the PI3K and STAT5 pathways
Cohesin regulates expression of genes that control differentiation, morphogenesis, proliferation, and pluripotency
Pathway analysis of transcriptome data in skin using Ingenuity Pathway Analysis® software suggested activation of both classical and alterative NFKB pathways
A schematic representation of the metabolic pathways of M. tuberculosis interrogated by qPCR is shown.
a | Cytoskeletal actin microfilament dynamics are affected by the activation of six classes of plasma membrane receptor: receptor Tyr kinases (RTKs), G protein-coupled receptors (GPCRs; with α-subunits of Gα12/13, Gαq/11 or Gαi/0), integrins as structural mediators of focal adhesions, transforming growth factor-β receptors (TGFβRs), E-cadherins at adherens junctions and Frizzled, which mediates the non-canonical Wnt–planar cell polarity (PCP) pathway involving Dishevelled (DVL)
a | Regulation of microRNA-1 (miR-1) and miR-133 by sereum response factor (SRF)
Functions of 14-3-3 in tumor-suppressor pathways
After photolysis, all-trans RAL is reduced to all-trans ROL by RDH in cone outer segment
We propose that exposure of pancreatic β-cells to high glucose, palmitate or cytokines leads to activation of Tiam1/Rac1 signaling axis culminating in the activation of Nox
Complement is activated by three major pathways
The action sites of staphylococcal enterotoxin B (SEB) and phorbol 12-myristate 13-acetate (PMA)/ionomycin, and major signaling pathway for interleukin-2 production are shown
TGF-β signaling pathway TGF-β is secreted in a latent form and activation is mediated by several molecules including furin and emilin
Since the discovery of leptin, understanding of the mechanisms that control energy balance has rapidly advanced
Upper half: Overexpression of IFNŒ± activates myeloid DC (mDC) to increase BAFF production
Binding of FGF7 to the FGFR2b (1) stimulates ADAM17 in a manner that can be blocked by inhibitors of Src kinases, p38 MAP-kinase and of phosphatidylinositol 3 (PI3) kinase, which is responsible for the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3) (2)
Proposed LNM (1) biosynthetic pathway featuring LnmKLM-catalyzed β-alkylation of the LnmJ PKS module-8 ACP-tethered intermediate in the S. atroolivaceus S-140 wild-type strain (path a) and processive elongation of polyketide intermediates tethered to the LnmJ PKS module-5 and module-8 ACPs as evidenced by accumulation of LNM K-1 (2), K-2 (3), K-3 (4), K-1′ (5), K-2′ (6), and K-3′ (7) in the S. atroolivaceus S-140 mutant strains SB3029 (i.e., ΔlnmK), SB3030 (i.e., ΔlnmL), and SB3031 (i.e., ΔlnmM) (paths b and c).
Three recently published papers identified multiple mechanisms of RAF inhibitor resistance using cultured cells and patient biopsy specimens (-)
A. Schematic of the canine ventricular cell model including Ca2+ handling, electrophysiology, CaMKII signaling pathway and βAR signaling domains.
A2AR and A2BR activation increase cyclic AMP (cAMP) levels with subsequent activation of the PKA → CREB pathway to increase transcription of cAMP-regulated genes, while A1R and A3R activation decrease cAMP levels
A variety of host and tumor interactions can promote angiogenesis
A model depicting interactions of putative nutrient and energy signaling components
Menin inhibits AKT signaling by association with AKT
(A)Cadherins, HEG1 and integrins are three transmembrane receptors connected to CCM proteins or functions
Working model of molecular mechanism(s) by which chronic Pb2+ exposure disrupts synapse formation and plasticity in developing hippocampal neurons
Oxidative pathways leading to neuronal cell death and glial cell inflammation: protective effects of resveratrol []
Sphingolipid effects on intrinsic and extrinsic apoptotic pathways
Effect of sphingolipids on the PI3K/AKT pathway
Signaling pathways explored in the last 5 years are summarized
Under ER stress, unfolded proteins accumulated in the ER activate ER sensor proteins PERK, ATF6 and IRE1
a| Moraxella catarrhalis and Neisseria meningitidis use specific virulence proteins to activate carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1), which co-associates with and inhibits Toll-like receptor-2 (TLR2) signalling
a| The indicated pathogens express mannose-containing ligands that bind DC-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN) and induce crosstalk with Toll-like receptors (TLRs) through RAF1 signalling
Porphyromonas gingivalis interacts with Toll-like receptor (TLR)-2 (specifically with the CD14–TLR2–TLR1 complex) and TLR4
Certain bacteria (such as Porphyromonas gingivalis, Mycobacterium tuberculosis and Bacillus anthracis) bind CD14 and induce Toll-like receptor-2 (TLR2)–TLR1 inside-out signalling for activating and binding complement receptor-3 (CR3), which leads to a relatively ‘safe’ uptake of these organisms by macrophages
Akt regulates numerous biological functions by phosphorylating distinct protein substrates
Activation of glia and neurons in the dorsal horn of the spinal cord after peripheral injury
Widespread extracellular matrix (ECM) pathway silencing by DNA hypermethylation in colon cancer
Gene expression changes in response to zebularine therapy in vivo
β1-adrenergic receptors activate multiple pathways in striatal neurons
Under excessive ER stress, the ER transmembrane sensors IRE1α and PERK send signals through the BCL-2 family of proteins to activate the mitochondrial apoptotic pathway
Cells may undergo apoptosis by two major pathways, an extrinsic receptor-dependent pathway and an intrinsic (mitochondrial) apoptosis pathway, in response to various acute injurious stimuli
Signaling stimuli trigger the generation of ROS, which in turn (i) activate MEK, phosphorylating ERK and (ii) activate RhoA/ROCK pathway, facilitating ERK nuclear translocation
The cAMP-PKA-CREB pathway, a signaling cascade that is critical for memory formation, induces expression of the genes encoding NR4A nuclear receptors
CXCL12 binds to CXCR4 and CXCR7, which are G protein-coupled receptors (GPCR) that can form homodimers or heterodimers
Small ubiquitin-related modifier (SUMO) undergoes processing by ubiquitin-like protein-specific proteases (Ulps) and sentrin-specific proteases (SENPs) to its mature form (step 1), revealing a carboxy-terminal Gly-Gly motif
a | Transcription factors, including nuclear factor-Œ∫B (NF-Œ∫B) inhibitor Œ± (IŒ∫BŒ±), are regulated through post-translation modifications
Post-translational modification of the processivity factor for eukaryotic DNA polymerases, proliferating cell nuclear antigen (PCNA), by ubiquitin-like modifiers results in the recruitment of specific proteins that otherwise display weak interactions with PCNA
Simplified schematics of the MAPK and PI3K pathways in melanoma and the clinical compounds available for their inhibition
Two distinct NF-κB activation pathways have been described
Combined function of Hmgb1 and Hmgb2 integrates the Hox-Shh pathway, Wnt/ß-catenin signaling and BMP signaling for proper development of digit 5 in the forelimb bud
Autophagosome formation requires two ubiquitin-like conjugation systems: the Atg8 (LC3) conjugation system and the Atg5–Atg12 conjugation system
A representative cascade of the TGF-β pathway
Normally, cell proliferation is controlled by growth factors binding to receptor tyrosine kinase with sequential activation of Ras → Raf-1→ MEK → ERK to induce cell proliferation
Mediators of the extrinsic pathway of PCD by Fas and TNFR-1 signaling
A mechanistic diagram showing how Notch could promote EMT progress
The rigid chaperone domain (Ch) of MESD binds to the newly synthesized BP domain of LRP6, serving as a folding template
(A) Two verbal models of fate specification in... (B) Schematic diagram summarizing interactions... (C) Fate plane in the model showing the criteri...
The left part of the diagram (in blue) depicts the mechanism of CICR, in which an action potential activates the voltage-dependent L-type Ca2+ channel, leading to a small Ca2+ influx
During hyperglycemia AR reduces glucose to sorbitol using NADPH as a co-factor and later sorbitol dehydrogenase (SDH) reduces sorbitol to fructose using NAD as a co-factor
Intracellular signaling by the leptin (LepRb - cyan) and insulin receptor (magenta)
Representation of genes of the vascular endothelial growth factor (VEGF) signaling pathway and the sites at which bevacizumab, sorafenib, sunitinib, brivanib, and cilengitide are known to act
The left side of the diagram depicts the classical TGFβR/Smad pathway
Ste5 coordinates signal activation in the yeast mating pathway
Diacylglycerol kinase (DGK) signaling in vascular smooth muscle contraction
BRB Array Tools was used to generate probesets differentially regulated at the P<0.05 level of significance.
Schematic model for the role of TGF-β signaling pathways in iTreg and Th17 cell development
Apoptosis: intrinsic, extrinsic, and endoplasmic reticulum (ER) stress mechanisms
Therapeutic effects can be monitored using DMR on scant cell populations
Model of the extracellular network of proteins that control D–V patterning
Regulatory role of ATM in cellular responses to DNA DSB repair
Model of the regulation for CD300B expression
Rationale for simultaneous targeting of SK and Raf for cancer chemotherapy
Clustering of the BCR induces the assembly of a signalsome at the receptor containing Syk, BLNK and BLNK-associated molecules
Differential requirement of STAT for RTK signaling
BAFF and APRIL signaling pathways in B cells
Oxidative stress induced by environmental toxicants activates the PI3K/c-Src/FAK pathway, which subsequently controls the phosphorylation of caveolin-1, TJ and/or AJ proteins, the stability of E3 ubiquitin ligase Hakai and the interaction of polarity proteins with the endocytic adaptor Numb
Bcl-2 as an attractive target for modulating different modes of cell death in cancer therapy due to close communications with mediators of apoptosis, programmed necrosis, and autophagy
Schematic explanation of cross-scale molecular target evaluation
(A) HER2 signal transduction. Acti... (B) Downstream activation of the P... (C) Accumulation of p95-HER2. The... (D) Increased signaling from alter...
(A) Lapatinib is a dual EGF recept... (B) Pertuzumab, a monoclonal antib... (C) HSP90 inhibitors promote HER2... (D) TDM-1, the antibody–drug conju...
GM-CSF activates the Ras/MAPK and the PI3-K/p70S6K pathways in hematopoietic cells, but at different rates
A. eCB-mediated I-LTD mediated is triggered by postsynaptic activation of group I metabotropic glutamate receptors (mGluR-I), leading to the production of diacylglyercol (DAG) by phospholipase C (PLC).
Various factors that regulate melanocyte function in the skin are shown
Detection of DNA and RNA in the lumen of endosomes by TLR9 and TLR7, respectively, triggers signal transduction cascades leading to the production of type-I interferons (IFN) and inflammatory cytokines
Examples of cellular receptors that sense infection and cell death
A. In arcuate neurons including those that express POMC, dopamine, and GABA, E2 activates the Gq-mER leading to activation of PLC-PKC-PKA pathway.
Transcription factor restricted functional interactions with ERŒ± in osteoblasts
(A) TLR-ERK-mediated induction of retinoic acid metabolizing enzymes and... (B) β-catenin signaling pathways in programming regulatory DCs. Activati...
Schematic representation of HER2-mediated PI3K-Akt signaling pathway
Neurodegenerative diseases are among the most common diseases and yet probing the pathological mechanisms has remained a challenge
Summary of the cascades of events triggered by CsA
(A) In dendritic cells, LPS induced TLR4 signaling occurs through both MyD88-dependent and -independent pathways
Diagram showing the interaction of the leptin and insulin signaling pathways in both the transcriptional regulation of Pomc and in the regulation of POMC procesing and the enzymes responsible for POMC procesing
Functional pathway analysis of the 28-gene prognostic signature using Ingenuity Pathway Analysis
Biochemical pathways leading to the synthesis of TAG and cholesterol
Growth signaling pathway affected by arginine deprivation in ASS(‚àí) cells which leads to autophagy
(A) In rodent neurons, EphA activation leads to inhibition of ERK with r... (B) In C. elegans, Eph homolog VAB-1 interacts with and inhibits PTEN ac...
Mitochondria-targeted neuroprotective interventions for acute injury to the immature brain
Display of differentially expressed genes in human myometrium during term labor mapped on the MetaCore Interleukin-17 signaling pathway
Summary of the CF signal transduction pathway
AdPLA is an adipose specific PLA2 that can produce arachidonic acid (AA) from the sn-2 position of membrane phospholipids
Connectivity of differentially expressed genes in the important signaling pathway following exposure of PCB 153 in human PBMC depicting the connectivity between genes expressed (‚â•1.0, t-test, p<0.001) and the important signaling pathways in human PBMC in vitro following exposure of PCB 153
Connectivity of differentially expressed genes in the important signaling pathway following exposure of PCB 138 in human PBMC depicting the connectivity between genes expressed (‚â•1.0, t-test, p<0.001) and the important signaling pathways in human PBMC in vitro following exposure of PCB 138
During chemotaxis, cAMP stimulates intracellular signaling through the cAR1 receptor and coupled heterotrimeric G-proteins (G)
Activation of mast cells initiates a cascade of events resulting in Th2 polarization and both positive and negative feedback regulatory loops
Schematic representation of the zif 268 pathway in spinal cord neurons
The three levels of regulation of the IGF-IR pathwayand its components
Kaempferol treatment in ovarian cancer cells inhibits Akt phosphorylation, which in turn inhibits expression of Bcl-xL gene but up-regulates expression of p53, Bad, and Bax genes, leading to an imbalance between pro-apoptosis and anti-apoptotic factors and in favour of activated Caspase 3/7 and intrinsic apoptosis
Pharmacological targets in the nitric oxide (NO)-soluble guanylate cyclase (sGC) signaling pathway in pulmonary hypertension
SnoN possesses both pro-oncogenic and anti-oncogenic activities
Schematic representation of TIRs signaling pathway
(a) Two-step scheme for metabolically engineering a cell surface with complementary chemical properties to bind to a custom-designed tissue engineering scaffold, as described in more detail in panels (b) and (c)
Schematic diagram of RHIM-dependent signaling
Generation of cGMP is shown from both a nitric oxide synthase (NOS) –soluble guanylate cyclase (sGC) pathway, and natriuretic peptide receptor-receptor GC pathway
Intracellular activation of AC converts ATP to cAMP resulting in modulation of activity in growth promoting pathways
The effects of IFNα involve at least two primary processes: (1) The first pathway involves the induction and release of cytokines/chemokines that mediate the recruitment of immune cells that induce autoimmune cell death
The activated BMK1 MAPK cascade promotes cell cycle progression of tumor cells induced by mitogens and/or oncogenic signals
Hypothetical localization of the different FA subcomplexes at a replication fork encountering an interstrand crosslink (red line)
A. Canonical replication checkpoint activated by a lesion on one strand of the DNA.
Activation of STAT1/3 by cytokine signaling promotes transcription through a STAT element
Basic intracellular molecular pathways regulating MN survival during development
Schematic diagram of the mTOR signaling pathway
DSBs are repaired by one of three pathways, c-NHEJ (left panel) HR (middle panel) or a-NHEJ (right panel)
The insulin/IGF-1 signaling (red ovals) and TOR (beige ovals) pathways may interact at multiple levels to ultimately regulate organismal lifespan
Mitochondria are known to signal to the nucleus by at least two mechanisms: one is the retrograde signaling pathway (RTG) that involves LST8 and possibly TOR; the other uses reactive oxygen species and signals through the JNK–FOXO pathway
the insulin/iGF-1 signaling pathway is conserved across phylogeny
Cells progressing to senescence acquire several prominent phenotypes and the levels of many proteins governing each of these phenotypes are influenced by senescence-associated miRNAs
aCGH data for the ninty-three ovarian tumors were analyzed by GenMAPP software
Cartoon representing CsA-mediated activation of TGF β1-dependent signaling leading to epithelial-mesenchymal transition in epidermoid carcinoma cells
Wnt signaling and regulation of β-catenin in tumorigenesis
The orange repressive arrows depict high-quality putative targets of miR-1 in the PIP3 pathway in cardiac myocytes (see Experimental Procedures)
Once cleaved from latent TGF-β binding protein (four isoforms, LTBP1-4) the mature and active dimeric TGF-β (three isoforms, TGFB1-3) can bind to heteromeric receptor complexes formed by type I (TGFBR1; ALK5 and ALK1 (activin A receptor type II-like 1)) receptors and type II (TGFBR2) receptors, initiating signal transduction
Both TGFβ and bleomycin activates PI3 Kinase-Akt-mTOR signaling pathway
The lack of functional CFTR on the cell surface dysregulates pro-inflammatory signaling via innate immune response (TNFa-IL1b-TLR) pathways resulting in NFŒ∫B mediated hyper-inflammation, and the chronic CF lung disease
Major intracellular signal transduction pathways for CRF1 and CRF2 receptors
A) Schematic outline of mitochondrial and metabolic pathways connected t... B) Metabolic and genetic checkpoints of progressive liver disease leadin...
Genes highlighted in red demonstrate a significant increase in expression in invasive cells compared to their non invasive counterpart
Graphical representation of the candidate genes involved in the pharmacodynamics of doxorubicin in a stylized cancer cell
The mammalian target of rapamycin (mTOR) signaling pathway
A) Spatial organization is necessa... B) Intracellular signaling pathway... C) Scaffold proteins also play an... D) Assembly line processes such as...
Pathway analysis links the differentially expressed gene signatures of the MED29 transduced Hs 700T and MIAPaCa-2 cells to a cellular network involved in cell cycle, cancer, and genetic disorder
The solid arrows represent pathway relationships that have been defined genetically by molecular epistasis analysis or that have been implied through pathway up- or down-regulation
Activation of the NMDA subtype of glutamate receptors (NMDARs) and voltage-gated Ca++ channels leads to influx of Ca++ and activation of the ras-MEK-ERK signaling cascade in adult neurons
Effects of ROS, exemplified here by H2O2, on the genesis and survival of both osteoblasts and osteoclasts are depicted in black, and as shown require the same signaling cascades and factors, i.e.
Apoptosis occurs via two molecular pathways, extrinsic and intrinsic
ROP proteins are delivered into the cell during and after parasite entry and differentially activate host signaling pathways
Schematic illustrating that AMPH indirectly stimulates dopamine (DA), glutamate (glu) and BDNF (B) release and stimulation of D1 dopamine, glutamate, and TrkB receptors, respectively, in the striatum
ERK-dependent signalling during conditioning and extinction of fear
(a) A gene network shows that mRNA levels of PD... (b) A network shows that transcripts of LOX gen... (c) A network composed of TGFβ- and ECM-related...
Cartoons of PAR-1-dependent signaling by APC and thrombin in endothelial cells when EPCR is either free or occupied by protein C
(1) N-linked glycosylation of PAR1 regulates surface expression and signaling
SMO is the key signal transducer of the Hh pathway
Bidirectional transcription of an mRNA (on the right in red) and a ncRNA (on the left in blue) is depicted as an example
Repair of a DNA double-strand break (DSB) is usually accomplished by either homologous recombination (HR) when a homologous chromosome is available in the form of a sister chromatid, or by non-homologous end-joining (NHEJ) throughout the cell cycle
A schematic diagram illustrates the signaling pathway for IKKβ-mediated Htt proteolysis
In the canonical pathway, Bmp ligands bind to type II receptors then activate type I receptors
Enzyme names are shown in yellow oval circles, and their interacting metabolites are represented in blue octagonal circles.Adapted with permission from [].
(A) Phenotypes were: moderate sensitivity (orange, mean fold change of I... (B) Modified 5-fluorouracil drug pathway highlighting the gene modulator...
The KATP channel determines, in part, the membrane potential of the smooth muscle cell and, hence, the contractile state
Model for Sulf regulation of Wnt signaling
Several key molecular components participate in the initiation, execution and completion of autophagy
Arrows and minus signs represent positive and negative regulatory effects, respectively
The “Bcl-2 family regulated” apoptotic pathway is initiated by cytotoxic stimuli, including DNA damaging agents and cytokine withdrawal, which perturb the balance between pro-survival and pro-apoptotic Bcl-2 family proteins within the cell, leading to activation of the downstream caspase cascade and ultimately apoptosis
Schematic representation of the proposed regulatory pathway
Maintenance of initiated cross bridge-cycling (by Ca2+/MLCK/phosphorylated-MLC20 or p-MLC20) in the sustained smooth muscle contraction or the basal myogenic tone depends on the mechanisms that inhibit MLCP
Molecular model of extranuclear functions of PV in promoting thyroid carcinogenesis via the integrin-FAK-cSrc signaling cascade
Solid arrows indicate the miR-7-regulated signalling pathway that is confirmed experimentally in the present study
Intrinsic and extrinsic apoptotic pathways
Drug combinations that would target the mTORC1 pathway with the concomitant inhibition of mTORC1-feedback loops
Negative regulation of the autophagy pathway
While TLR2 and 4 recognize viral pathogens on the plasma membrane, TLR3, 7/8 and 9 recognize viral RNA or DNA in the endosome
The recognition of viral RNA or DNA in the host cytosol activates downstream signaling, resulting in the production of type I IFNs and proinflammatory cytokines to limit viral replication and propagation
Possible pathways to androgen independence and the involvement of ANG
Schematic representation of the PI3K/mTOR signaling pathway highlighting the phosphorylation sites tested in our cellular and biochemical assays
A summary of the extracellular interactions between Wnts, Wnt receptors and Wnt regulatory proteins
Induction of DSB leads to lessening of torsional strain and unwinding of DNA superhelical structure which triggers local decondensation of chromatin and recruits the MRE11, RAD50 and NBS1 proteins (MRN complex), as well as BRCA1 to the DSB site (A, dashed arrows)
DNA damage (induction of DSBs) triggers activation of ATM () which in turn phosphorylates Chk2 on Thr68 causing its dimerization
RTKs, activated in response to growth factor signaling, initiate PI3K signaling
Activation of EGFR signaling increases HIF-1Œ± protein synthesis under normoxic conditions through the PI3K/AKT signal pathway
Signaling pathway from TCR engagement to gene expression in nucleus
A model for the proposed molecular pathways in arterial, venous and lymphatic specification in a developing embryo
Synaptic NMDARs are capable of signaling through the CaMKs and the Ras/Raf/MEK/Erk/Rsk2 pathway to phosphorylate CREB and initiate transcription of a variety of pro-survival genes
Changes in synaptic activity drive homeostatic compensatory changes in the number of surface AMPARs at synapses
Regulation of TGF-β responses by Egr-1 and its inhibitor
mTOR signaling cascade in the pathogenesis and prevention of skin cancer
Convergence of mTORC1 and GSK3-β in LPS-stimulated cells
Proteins inhibited by two or more RTKIs and the indicated pathway inhibitor(s) are grouped by protein function
In part A, the neuron expresses NAAG synthetase I (NAAGS I), an enzyme that mediates the synthesis of NAAG but not NAAG2
(A) Schematic representation of the Wnt pathway, with key phosphorylatio... (B) Chemical structures of the Wnt pathway inhibitors IWR-1, IWR-3, and...
Ethanol signaling pathway that initiates neural crest apoptosis
Analysis of p53 target genes in melanocytes treated with Nutlin-3 for 18 h
Molecular mechanisms in hereditary cancer
A total of 60 validated genes were analyzed for any reported association with genes belonging to apoptosis signaling and/or cell cycle and proliferation networks in Ingenuity Pathway Analysis
(A) A bulky DNA lesion is recognized by XPC-RAD23B, which binds to the undamaged strand of DNA, allowing for the recruitment of TFIIH (B)
Selected genes involved in inflammation (1) increase formation of DNA and protein-damaging reactive oxygen species (ROS), and (2) inhibit apoptosis while (3) simultaneously promoting increased cellular proliferation in a reactive molecular environment
Schematic representation of nicotine signal transduction pathways
Based on our results presented here, and together with results reported previously by our group and others, we propose that CXCR4-TCR heterodimer appears to signal in T cells in response to SDF-1 via the signal transduction pathway model shown in SDF-1 treatment induces the formation of the CXCR4-TCR heterodimer which mediates the activation of Gi proteins and ZAP-70 and this either directly or indirectly leads to the activation of several PLCs including both PLC-γ1 and PLC-β3
Hypoxia regulates other critical pathways that impact tumor progression in a HIF-independent fashion
Roles of NF-Œ∫B-mediated inflammatory pathway in cellular transformation, cancer survival, proliferation, invasion, angiogenesis and metastasis
Signaling pathway leading to signal transducer and activator of transcription (STAT)-3 activation (see text for definitions of abbreviations)
The central components of three pathways are shown (arrows, activation; bars, repression)
Possible mechanisms that sorafenib and PI-103 differentially inhibits and activates key kinases in the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways
Upon growth factor stimulation and subsequent activation of receptor tyrosine kinases (RTKs), class IA PI3Ks, consisting of p110α/p85, p110β/p85 and p110δ/p85, are recruited to the membrane via interaction of the p85 subunit to the activated receptors directly (e.g.PDGFR) or to adaptor proteins associated with the receptors (e.g.
Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer
Panel (A) depicts the pathogenic steps that bacteri... (B) illustrates host mechanisms employed to c... (C) demonstrates antigen-dependent (MHC prese...
Alternative signaling pathways that involve Ras/Raf/NF-Œ∫B as key players in reactivation of different viruses are depicted
PI3 kinases, heterodimers composed of p85 regulatory and p110 catalytic subunits, phosphorylate phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3), which leads to recruitment and activation of AKT
The B-cell receptor signaling pathway is initiated through phosphorylation of co-receptors IgŒ± (CD79a) and Igβ (CD79b), recruiting the tyrosine kinase SYK
In macrophages, LPS induces HIF protein synthesis and stabilization in a TLR4/MyD88-dependent fashion
GDNF dimerizes and binds to the GFRŒ±-1/RET receptor complex
Two different pathways regulating microsomal triglyceride transfer protein (MTP) expression have been proposed
EGCG regulates inflammation and joint degeneration by modulating MAPKs, AP-1, NF-Œ∫B pathway and STAT signaling activated by TNF-Œ±, IL-1β and IFN-γ in various cell types
ER activation of mGluRs is organized via caveolins into brain region specific functional microdomains
The network diagram depicts the coordinate regulation of GRE-containing transcripts involved in T cell receptor signaling
This network represents transcripts that involved in G protein coupled receptor signaling pathways
Cross-talk between TLR4 and IL-1 signaling pathways
Schematic illustration of pathway alterations involved in the development of low-grade serous carcinoma
ERM proteins are scaffolds for cAMP signaling pathways
Composite cytokines of CLF1 and CLC or CLF1 and the p28 subunit of IL-27 are assembled in the cell and secreted
Functional inactivation of pRB has been shown to result in numerous changes, including transcriptional changes (local effects: regulation of specific transcriptional activators: E2F, etc; broad effects: regulation of heterochromatin formation, including telomeric and centromeric regions; and global effects: chromosome condensation and cohesion levels [purple box, top right])
Control of transcription and miRNA biogenesis by TGF-β/BMP signaling
Extensive feedback and feedforward loops between Ras signaling and miRNAs
Upon EGF or TNF stimulation, PI3K/AKT, IKKβ and RAS/ERK pathways are activated
Schematic illustration of a representative immune response pathway that leads to the disruption of viral release from the plasma membrane
RANKL rapidly activates the classical (canonical) NF-Œ∫B pathway consisting of activation of the classic IKK complex (NEMO-IKK2), degradation of IŒ∫BŒ±, and release of p50/p65(RelA) dimers for translocation to the nucleus
A. Activated ARF6 facilitates tumor cell invasion by promoting invadopodia formation and microvesicle shedding.
Cholesterol synthesized in the endoplasmic reticulum (ER) by HMG CoA reductase (HMGCR) or internalized via scavenger receptors (CD36, SR-A) or low density lipoprotein receptor (LDLR), is assembled into nascent rafts in the Golgi apparatus for caveolin- and Niemann Pick C1 protein (NPC1)-dependent transfer to the plasma membrane
Schematic depiction of how complement modulates T-cell immunity
Model illustrating interrelations of insulin, PKCŒ¥ and arsenite
Notch signaling between adjacent cells functions to diversify cell fate: selecting progenitor cells which will maintain pluripotency, and cells which will terminally differentiate
Rice innate immunity signaling pathways [,,,]
PPAR-controlled fatty acid transporters CD36 and FATP import fatty acids into the hepatocyte ()
Hypoxia suppresses signaling for translation initiation, elongation, and ribosome biogenesis via concomitant inhibition of eIF2Œ± eEF2, and mTOR downstream targets 4EBP1, p70S6K, and rpS6
Simplified diagram illustrating the mTOR signaling pathway
A murine model of the multiple actions to suppress immune surveillance of exosomes released from neoplastic cells
Functional pathway analysis of the 12-gene genomic instability signature using Ingenuity Pathway Analysis
Local recycling of receptors through endosomes occurs at axon tips and in the soma as well as in dendrites
Activation of the Rb pathway during senescence restricts B-sMyb action at multiple levels
Solid lines with arrows show the activation or phosphorylation of proteins
Putative signaling mechanisms for apelin’s regulation of insulin sensitivity
The interaction of the EGF and TGF-β pathways in the control of proliferation in breast cancer (see also )
By regulating EGR1, c-JUN and EZH2 expression and activities, PTEN loss suppresses AR transcription factor activity and output, leading to reduced prostate epithelial differentiation and survival
Model for the role of TAK1 signaling in bone metastasis
Adolescent cocaine exposure regulated the mRNA expression of many genes involved in Wnt signaling pathways
Multiple TYRO3-activated pathways signaling pathways converge with transcription or activation of MITF (reproduced from Mitra et al ()), an oncogenic transcription factor often dysregulated in malignant melanoma
It is generally accepted that Notch signalling integrates multiple pathways, thereby tuning downstream expression to match the cell’s current needs and situation
The biological network of genes within the type-I interferon-signaling pathway is shown
Model of TGFβ signaling during PE cell EMT
(A) T-bet is a key regulator of the Th1 differentiation of CD4+ T cells.... (B) T-bet is involved in the early induction of IFN-γ in the development...
IFN-α (type-I IFN) and IFN-λ (type-III IFN) signal through distinct receptor complexes, but activate the same intracellular signaling pathway
The IRE1Œ±-XBP1 pathway in glucose homeostasis
NAD+-dependent histone deacetylase (HDAC) activity in relation to gene transcription
Sirt1 activity as it relates to AD etiology
A. Models for NF90’s action on cyclin T1 translation.
(A) Smooth transcriptional waves of cyclic gene expression sweeping through the zebrafish PSM (shown in blue)
4E-BP: 4E-binding protein; Akt: Protein kinase B; eIF4E: Elongation initiation factor 4E; IRS: Insulin receptor substrate; mTOR: Mammalian target of rapamycin; PI3-K: Phosphatidylinositol 3-kinase; Raptor: Regulatory associated protein of TOR; Rheb: Ras homolog enriched in brain; Rictor: Rapamycin insensitive companion of TOR; S6K: P70 S6 kinase; TSC: Tuberous sclerosis complex.Reproduced with permission from [].
Shown are key factors mediating the three known pathways of high-affinity iron uptake in this organism: reductive iron uptake, siderophore-iron uptake, and hemoglobin-iron uptake
Short dsRNA’s or 5’-triphosphate ssRNA’s activate RIG-I which associates with mitochondrial IPS-1 to trigger FADD/RIP1 (innateosome) controlled activation of the type I interferon genes
The steps leading from detection of RNA by RIG-I and MDA-5 through signaling and transcription of IFN genes are depicted
TGF-β ligand activation of specific cell surface serine-threonine kinase receptors activates the SMAD cascade, resulting in transcriptional activation of the GLI2 gene
The divergence of canonical Wnt/β-catenin signaling or non-canonical Fz/PCP signaling relies on Dvl protein
In the classical pathway (solid gray arrow), C21 precursors (pregnenolone and progesterone) are converted to the C19 adrenal androgens DHEA and androstenedione (AED) by the sequential hydroxylase and lyase activity of CYP17A1
Panel A, MyD88-dependent TLR signaling pathway is regulated by miR-146a
The yellow boxes represent the mAKAPβ signalosome
Crosstalk between host autophagy and viruses
Schematic diagram illustrating the proposed signaling pathway involved in cigarette smoke extract-induced increase in expressions of inflammatory genes in airway smooth muscle cells
Model showing the role of AKAP-Lbc in the regulation of cardiac hypertrophy, through the PKD-HDAC5-MEF2 signaling pathway
Simply comparing and contrasting the expression patterns of perturbed genes was inadequate for deciphering the MAPK pathway response dynamics
The initiation of autophagy is controlled by the ULK1 kinase complex that integrates stress signals from mTORC1
This figure illustrates the core TSC-mTor pathway, as discussed in the text
Pathway analysis of altered gene expression during pressure overload hypertrophy
Known and newly proposed pathways for kaempferol’s effect on angiogenesis in ovarian cancer cells
The RLR signaling pathway showing RIG-I bound to ligand RNA and signaling downstream to IRF-3 and NF-kB to induce IFN-Œ±/β production from a virus-infected cell
Overview of Intermediary Metabolism in the Heart
Intracellular signaling pathways integrate dopamine and glutamate signals
This network was identified as operative in Immune Response, Cell-to-Cell Signaling and Interaction, and Hematological System Development and Function, as determined by Ingenuity Pathway Analysis software
Schematic Overview of Nodal and Cripto-1 Signaling Pathways
PCa cells are characterized by exacerbation of lipogenesis associated with hyperactivation of mTOR pathway
(Panel A) Effective cancer therapy may require combination treatments. A put... B) A novel strategy to eliminate CSCs could be to induce their differ...
The relationship between Ras-driven signaling pathways, ROS, Hsp90, and ER stress
Mechanisms of estrogen hormone actionEstrogens mediate their responses through estrogen receptors (ERs) via multiple methods
Overview of the NF-Œ∫B activation pathways and the impact of S-glutathionylation
The phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling pathway () is one of the most aberrantly activated survival pathway in cancer, making it an important target for drug development., This pathway is negatively regulated by the tumor suppressor protein PTEN
The biosynthesis of TAG begins with the sequential acylation of glycerol-3-phosphate (G-3-P) by sn-1-glycerol-3-phosphate acyltransferase (GPAT) to produce lysophosphatidic acid (LPA) and by acyl-CoA:1-acylglycerol-3-phosphate acyltransferase (AGPAT) to produce phosphatidic acid (PA)
The apoptotic pathway to cell death from the perspective of the Bcl-2 family of proteins.1, The intrinsic pathway is initiated by various signals, principally extracellular stimuli
Axon injury triggers elevation of axonal Ca2+ by several mechanisms
A model of the role of sphingosine kinase localization on substrate utilization and delivery of S1P to specific sites for secretion or loading of intracellular effectors
In obesity, a local inflammation in heart increases macrophage and cytokine levels, such as IL-6, that affect myocardial glucose metabolism
Reduced expression levels of Progranulin (GRN) are present from early embryonic life
Proposed pathway for the interaction between estrogen receptor (ER)Œ± and growth factor (GF) and growth factor receptor (GFR) signaling pathways and regulation by estradiol (E2) and progesterone (P4)
Proposed pathway for the interaction between estrogen receptor (ER)Œ± and growth factor (GF) signaling pathways and regulation by estradiol (E2) and genistein (Gen)
In non-stimulated cells, cIAPs bound to TRAF2 ubiquitinate and degrade the kinase NIK thereby inhibiting the non-canonical NF-Œ∫B pathway
A generic model of fluid flow mechanotransduction modulation of vascular SMC gene expression and function
Oral epithelial cells are able to discriminate between the two morphological forms of C. albicans via the MAPK pathway using a biphasic response.
During inflammation, MMP9 expression is elevated and we have shown previously that MMP9 activates Notch1
BAD pathway in genes associated with induced cisplatin-resistance
Signaling pathways that regulate mammalian autophagy
The blue shaded area is a simplified summary of presumed ALK-1 and ENG signaling via TGF-β and BMP-9 in endothelial cells (EC); the genes mutated in HHT are circled
Wnts bind to their frizzled receptors (FZ) and coreceptors LRP in the membrane
TGFβ1/SMAD3 signaling as an integrator of fibrotic mechanisms in the kidney
Highest confidence network of genes influenced by CLOCK knockdown
Constitutively high MEK/ERK activity can mediate AR downregulation, growth inhibitory signaling and differentiation
(left) Nucleic acid sensors that respond to viral infection detect viral nucleic acids as foreign, thereby leading to the production and action of IFN
PRL crosstalk with estrogen, progesterone, EGF/TGF-Œ±, and IGF-I
Schematic representation of the EP4-mediated classical pathway and the EP4-mediated anti-inflammatory pathway
A model depicting the pathway of TGFβ-mediated Bim regulation and apoptosis
Signaling through a transmembrane receptor activates the PI3K signaling network to phosphorylate Akt and promote cell proliferation and invasion through mTOR
Targeting the PI3K/Akt/mTOR pathway to treat lymphoma
The VEGF Signaling Pathway within endothelial cells
Normally, the target of rapamycin (TOR) pathway is activated by nutrients (Glucose and amino acids), growth factors and insulin, which enhances the activation downstream of the transcription factor nuclear factor kappa B (NFŒ∫B) that is critical regulator of the pro-inflammatory gene expression
An array of cellular stressors can perturb the folding environment in the endoplasmic reticulum (ER) leading to unfolded or misfolded protein
In the resting state, β-catenin is phosphorylated by GSK-3β and rapidly degraded by the proteasome pathway
Proposed anti-WNV signaling pathways in mosquitoes
A) BMP-2 induces both Smad and MAPK signaling w... B) Wnt5a induces TnW through p38 and requires a... C) Oscillatory fluid flow induces MAPK signalin...
A pool of survivin is recruited to mitochondria, mostly of tumor cells and released in the cytosol in response to cell death stimuli
Schematic biosynthetic pathways for the major phospholipid (Kennedy Pathway) and sphingolipid classes biosynthesized in mammalian cells and observed in MALDI IMS of mammalian tissues
(1) Toll-like receptors (TLRs) are activated upon recognition of pathogen associated molecular patterns (PAMPs)
(A) Diagram of hippocampal circuitry. Red arrow... (B) Differential synaptic plasticity on CA2 pyr... (C) Cartoon model of a dendritic spine from CA2...
Pathways of binding, internalization and processing by immunotoxins and ADCs leading to the killing of target cells
The cytosolic calcium concentration [Ca2+]c can be increased (fat upward arrow) by either calcium influx from the extracellular space through the voltage-dependent calcium channel (VDCC) or N-methyl-D-aspartate (NMDA) glutamate receptor on the plasma membrane (PM) or by calcium release from the endoplasmic reticulum (ER) through either the inositol 1,4,5-trisphosphate receptor (InsP3R) or the ryanodine receptor (RYR)
A. Neurons expressing NAAG synthetase I (NAAGS I) mediate the synthesis of NAAG but not NAAG2. I... II) may release both NAAG and NAAG2.
BMP signaling pathway: BMP binds heterodimeric receptor to activate Smad proteins, which transactivate osteoblastogenic genes either directly or via Runx2
B cells develop in the bone marrow and migrate to the periphery
Signaling via the BCR and BAFF-R are both critical for B-cell maturity and homeostasis
Both BAFF-R and CD40 signaling utilize TRAF molecules to promote activation of NFŒ∫B
Schematic overview of the Nucleotide Excision Repair (NER) pathway
Endothelial cell, astrocytes and microglia are a prominent source of CXCL10 and CXCL9
NMDAR receptor signalling can be triggered by glutamate released from the presynaptic neuron or through the NMDAR agonist quinolinic acid (QA), a product of tryptophan metabolic pathways in microglia
BDNF and NGF levels are reduced in both HD and AD
Upregulation of autophagy is an efficient way to clear disease proteins in AD and HD, and therapeutic interventions have been tested against a variety of different targets
BDNF binds to the TrkB receptor, resulting in the phosphorylation of two tyrosine sites (Y515 and Y816) on the intracellular domain of the TrkB receptor
APC gene or activating mutations in β-catenin, result in the accumulation of β-catenin and subsequent complex formation with TCF/LEF transcription factors
Recognition of microbes in the intestinal mucosa
A, In the presence of Pak-1, ISO stimulation of the β-adrenercic receptor activates protein kinase A (PKA) signaling via activation of heterotrimeric G protein (α, β, and γ) and adenylate cyclase (AC)
FGF receptors signal through the evolutionarily conserved SHP2/RAS/ERK pathway to mediate biological responses
The present findings, together with our previous results on an interaction between Twist1 and EphA4 (), place Twist1 at the top of a regulatory hierarchy, controlling two independent pathways, Jagged1/Notch and ephrinA-EphA
Intracellular GSH balance is maintained by de novo synthesis, regeneration from GSSG, and extracellular GSH uptake
The network is composed of several pathways coordinately promoting tip-targeted exocytosis and positive and negative feedback loops, which may balance each other to maintain a certain size of the apical ROP1 cap that defines tip growth domain or may allow the oscillation of the ROP1 activity
LPS-induced cytokines are triggered by TLR4 and are dependent in part on the MyD88 pathway and/or the MyD88-independent TRIF pathway
SRF regulates PRGs by virtue of association with different cofactors
Ingenuity pathway analysis of phosphatidylinositol 3-kinase (PI3K) signaling pathway affected by angiotensin II
Schematic of the sonic hedgehog signaling pathway in the primary cilium
In macrophages, P. gingivalis interacts with the CD14/TLR2/TLR1 receptor complex ().
[A] The base excision repair model for expansion
Proposed model in which Mad and Medea bind to the Wg Pangolin-Armadillo transcriptional complex in the absence of BMP signals
All dotted lines denote hypothetical pathways
Proposed estrogen receptor (ER)-activated signaling pathways involved in vasodilation
PC, phosphatidylcholine; PE, phosphoethanolamine; PS, phosphatidylserine; PLD, phospholipase D; PLA1/2, phospholipase A1/2; PA, phosphatidic acid; LPC, lysophosphatidylcholine; LPA, lysophosphatidic acid; MAG, monoacylglycerol; LPP, lipid phosphate phosphatase; LDL, low-density lipoprotein; ATX/lysoPLD, autotaxin/lysophospholipase D; AC, adenyl cyclase; cAMP, cyclic adenosine monophosphate; ROCK, RhoA-associated kinase; SRF, serum response factor; PLC, phospholipase C; PKC, protein kinase C; PI3K, phosphoinositide 3-kinase; MAPK, mitogen-activated protein kinase; eNOS, endothelial nitric oxide synthase
The signaling components of the RAS/MAPK pathway found to harbor activating mutations in various types of nevi and melanoma
In early-mid-stage atherosclerotic lesions, insulin resistance is associated with a decrease in eNOS activation and NO production and increase in VCAM-1 expression by arterial ECs
Inflammatory cytokines up-regulate SGPG expression by stimulating GlcATp, GlcATs, and HNK-1ST genes via NF-Œ∫B activation
The schematic depicts the PKR pathway that is initiated following virus infection
Glutamate released from corticostriatal projection neurons stimulates NR1A/NR2B NMDAR and mGluR5 receptors on striatal medium spiny neurons (MSNs)
(A) In the amyloidogenic pathway, APP is first cleaved by β-secretase (β-sec, BACE), leading to a secreted ectodomain, sAPPβ and a membrane bound fragment, C99
Pathway diagram of key effectors involved in glial neoplasia initiated by EGFR and PI3K in Drosophila, showing the pathway circuits driving cell cycle entry and progression, and protein translation
Working model describing how in HIV+ macrophages constitutively activated PI3K elicits blunting of lipid A-induced increases in TNFŒ± release through sustained mTOR activation
Pathway Studio® (Ariadne Genomics) was used to identify known relationships among human homologues of the genes identified as differentially regulated by ANOVA
The contribution of chemoattractant GPCRs to glioma stem-like cell mediated tumorigenesis, invasion and angiogenesis express various GPCRs
(a) Th17 cells from blood a... (b) Th17 cells express poly... (c) Th17 cell-derived IL-17... (d) These chemokines recrui... (e) Treg cells are enriched...
Early Growth Response 1 (EGR1) activation is achieved through multiple receptor-dependent signal transduction pathways downstream of both the Ras oncogene (via the MAPK pathway) and Phospholipase C (PLC; via protein kinase C)
Genomic and nongenomic vascular effects of estrogen
Several types of TG2-containing adhesive / signaling complexes present on the cell surface
E-cadherins, integrins or guanylyl-nucleotide-binding protein (G protein)-coupled receptors (GPCRs) activate SRC, which phosphorylates focal adhesion kinase 1 (FAK1)
Scheme of the functional role of FGF signaling in neural specification of hESCs
Arginine is synthesized endogenously from citrulline primarily via the intestinal-renal axis
Upon engagement of a ligand by the inhibitory receptor, the tyrosine residue of inhibitory motif ITIM is phosphorylated so as to recruit the lipid phosphatase SHIP or the tyrosine phosphatase SHP-1 or SHP-2
MUC1–ICAM-1 interactions regulate different heterotypic cell– cell adhesions
The molecular mechanisms by which IL-27 promotes Foxp3‚àíIL-10+Tr1 cell differentiation and represses TH17 cell development through activation of Stat1 and Stat3 activation are shown
Developmental pathways in Saccharomyces cerevisiae
In macrophages, P. gingivalis is recognized by the CD14/TLR2/TLR1 receptor complex ).
The initial step of PGE2synthesis is the stimulus-induced liberation of AA from the membrane phospholipids by PLA2 enzymes
IFN-αβ induced by viral infection or TLR agonist poly(I:C) induces expression of IL-15 and up-regulation of MHC I. Up-regulation of MHC I enhances presentation of self and virus-encoded peptides, which signal through the TCR of bystander CD8 T cells, inducing Eomes expression.
Retinal progenitor cells (RPC) express characteristic genes including Rax, Pax6, and Chx10, and appear to remain proliferative and undifferentiated, at least partially, under the influence of Notch activity
Pathway adapted from  by including three missed edges and correcting one reversed edge
Networks inferred by choosing associations with u1 ∈ (0.3, 0.4), u2 = 0.1, u3 ∈ (0.3, 0.5), and uf ≥ 0.8 in five MCMC runs of the HM on the simulated data with constant
PA can be generated de novo,, by sequential enzyme-catalyzed acylations of glycerol-3-phosphate, or in response to cell signaling pathways ()
G protein-coupled receptors (GPCR) trigger dissociation of GŒ± and Gβγ heterotrimeric G proteins upon agonist stimulation
Elevation of interleukin 6 (IL6) during inflammation stimulates hepcidin transcription through binding to the IL6-receptor (IL6R)-gp130 complex, which stimulates signaling through the phosphorylation of JAK leading to the phosphorylation of STAT3
Clopidogrel activation and platelet aggregation pathways
(A) Model for the relationship of the innate immunity and wound closure... (B) Possible mechanism of small GTPase regulation in wound healing.
Metabolic pathways, transport, and receptors of S1P
Schematic diagram shows the possible effect of xanthones on the apoptosis pathways
Presynaptic: The active zone (AZ) is indicated by a T-bar
Molecular mechanisms of FGFR3 signaling in cartilage
A proposed model for the LMW-HA-induced CD44 interaction with TLRs and MyD88/NF-Œ∫B signaling in breast tumor cells: The interaction between LMW-HA and CD44 induces a multi-molecular complex containing CD44, AFAP-110, TLR2/TLR4 and MyD88 (step 1) which then promotes AFAP-110-F-actin binding and cytoskeleton activation (step 2) resulting in tumor cell invasion
The activity of AMPK can be modulated by the AMP:ATP ratio or triggered by the biguanide metformin, resulting in inhibition of mTORC1 as well as augmentation of fatty acid oxidation and increased transcriptional activity of FOXO protein
(A) Pten/Braf/Bcat-STA melanomas are characterized by rapid growth, high degree of melanocytic differentiation, and extensive metastasis
Sarcolemmal actin assembly and nuclear signaling
mTOR regulates many cellular activities through two distinct complexes; mTORC1 and mTORC2
In addition to its numerous actions in the nucleus, SIRT1 also has some newly discovered cytosolic targets
Schematic representation of the mechanism of late PC
The HER network, recently described in systems biology terms, is a robust redundant network comprised of an input layer of 4 membrane (M) tyrosine kinase (TK) receptors (HER1/EGFR-HER4) and multiple ligands [e.g., EGF, TGFŒ±, amphiregulin (AR), and heregulins (HRG)]; a signal core processing layer involving a series of phosphorylation (e.g., activation of the PI3K/AKT, RAS/MEK/MAPK, and STATs kinase cascades) that transmit signals from the receptor layer to the output layer; and an output layer of transcription and coregulator factors (TF, CoReg) that function in the nucleus (N) to alter expression of genes regulating tumor cell proliferation, survival, and other characteristics of the malignant phenotype (, ).
Intercellular communication between adjacent epithelial cells via cell–cell signaling receptors
(A) Summary of S-1-P src activation pathways in VSMC: S-1-P-mediated src... (B) Summary of S-1-P signaling in VSMC: S-1-P interacts with G-protein-c...
Tyrosine kinase inhibitors (monoclonal antibodies and small molecules) block RTK/Ras signaling upstream of the PI3K-Akt-mTOR axis
The presence of mutant SP-C protein in the ER induces the dissociation of BiP from three proximal sensors, IRE1, ATF6, and PERK to initiate transcription factor cascades for chaperone induction or translation attrenuation
Lipid-poor apoA-I or its mimetic peptides bind directly to ABCA1 or a closely associated protein (step 1) that rapidly stimulates JAK2 autophosphorylation (step 2)
The beta2-adrenergic receptor and CD86 signaling pathways converge to induce an increase in the level of IgG1 produced by an activated B cell
Beta2-adrenergic receptor engagement on a B cell that will make IgE uses a unique signaling pathway to increase the level of IgE produced
Ischemic preconditioning (IPC): signaling pathways and targets
Arf and Arl function in the secretory pathway and in specialized transport
The PI3K/Akt signaling pathway is involved in several human cancers
Schematic illustration of the mechanisms that lead to cell survival in MEN2A associated RET mutations that activate PI3K/Akt signaling: apoptosis suppression and enhanced cell cycle progression
Bioenergetic regulation of cellular physiology and gene expression
Metabolic, redox, and epigenomic influences of the ketogenic diet
Aldh1a2 is the main RALDH isoform expressed in gut-associated DC, although Aldh1a1 and Aldh1a3 have also been described in other gut-associated cell types, such as IEC and stromal cells
The overlay of significant canonical pathway and the connectivity in the molecular mechanism of cancer, with the eight genes in IPA canonical pathway and with the genes in Network (I) that differentially altered in PCB exposure
Schematic mechanisms of hypoxia-induced collagen deposition
AMPK is activated when AMP and ADP levels in the cells rise due to variety of physiological stresses, as well as pharmacological inducers
LKB1, the upstream kinase for AMPK, is the tumor suppressor gene mutated in Peutz–Jeghers syndrome (PJS), as well a significant fraction of sporadic lung cancers and cervical cancers
AMPK regulates several physiological processes through phosphorylation of transcription factors and co-activators
Migration of marginal zone precursor B cells regulated by type I interferon (IFN) and IL-17
Modulation of oxidative stress is a central process in the development of obesity-induced insulin resistance
PGE2synthesis is initiated by the (glucocorticosteroids sensitive) phospholipase A2-driven release of arachidonic acid (AA) from cell membranes
MODEL OF FOLATE-ALCOHOL AND CANCER PATHWAY HYPOTHESES
Model demonstrating CREM Œ± activation by cAMP pathway and subsequent binding on the CRE site of the SYK promoter to result in downregulating SYK expression in normal T cells
The right side is for the signal cascade in the cell cycle G1/S checkpoint signaling pathway while the left side is for the P53 signaling pathway
Ingenuity pathway analysis (IPA) of the EGFR ablation signature with oncogenic (A) and wildtype Ras (B)
The TLR4 signaling pathway is highly regulated
RAS is activated by receptor tyrosine kinase (RTK) activation with several ligands that invoke these intermediates
AngII binds the AT1 receptor to activate phosphoinositide-specific phospholipase C (PLC)-mediated cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3)
Best-fitting Independent pathway model, showing one twin in a pair: circles indicate variance components, and rectangles indicate observed variables
(A) Autoradiograph showing representative sections of typical protein array phosphorylation assays performed using the four viral kinases
The contribution of TIP60 activation by the conserved herpesvirus kinases to lytic replication as illustrated mechanistically for EBV-infected cells
Schematic representation of prominent signaling pathways involved with PDAC tumoral compartment and stromal compartment crosstalk
IRF signaling pathway that was generated from pathway analysis of proteins with significant fold changes across both studies
Gal-1P (an intermediate) and galactitol (a by-product) of the blocked galactose metabolic pathway interfere inositol turnover and inositol entry by inhibiting IMPase and SMIT, respectively
Engulfment of apoptotic cells activates several pathways that may affect phagocyte metabolism and promote continued corpse uptake
Known components of the PCP signalling pathway and related cellular functions
Factors shown to promote or inhibit the vascular normalization phenotype in tumors
A.) The role of S1P in leukemia. B.) S1P signaling and apoptosis in lymphomas. C.) S1P signaling and apoptosis in Multiple Mye...
Seventeen genes are known to be involved in the “gemcitabine metabolism pathway”
ATM interaction with metabolic signaling pathways
ATM regulates mTORC1 activity through AMPK in response to elevated ROS levels
(a) Newly synthesi... (b) After geranylg... (c) Free prenylate... (d) Several RHO GT... (e) The rate of cy... (f) Once at the me... (g) Active RHOA ca...
JNK signaling enhances the compensatory proliferation of the neighboring cells, stem cells or cancer stem cells (CSCs)
Model of the host cell EGF signaling pathway and proteins downstream of the EGF receptor that are activated in response to C
N-glycan biosynthetic pathways in eukaryotes and glycoengineering
Diagram of IGF/INSR/IGF1R signaling pathway
The illustration of the effects of mitochondrial ROS induced by NADH on the INa
Signal transduction events that link ER stress to inflammation
Putative role of the mTOR pathway in pathogenesis and epileptogenesis of focal cortical malformations
Pyruvate kinase isoform M2 is expressed in proliferating cells, where it can exist both as a high-activity tetramer and a low-activity dimer
Examples of previously known and predicted biosynthetic pathways containing amidoligases are shown
Schematic of the PTEN/mTOR signaling pathway
The canonical Wnt/β-catenin and non-canonical Wnt signaling pathways
(A) LFS-LTD in 10 μM of the diacylglycerol lipase inhibitor THL
In the absence of a Wnt signal the destruction complex including Axin, APC and the kinase GSK3, phosphorylates (P) β-catenin
(A) SOX and TCF... (B) SOX and TCF... (C) SOX might s... (D) transcripti... (E) co-activato... (F) SOX protein... (G) Some SOX pr... (H) Sox and Wnt...
Shown is the subnetwork with IGFBP-3 and the full PSN (main view and inset, respectively)
The BH3-only proteins Bim and Bmf are subjected to multiple layers of regulation
Cell death signalling regulated by the Bcl2 family
Myostatin and activin signaling in muscle
Pathogens are recognized by the host APCs through TLRs, which induce intracellular signaling mainly through two adapter molecules, myeloid differentiation factor 88 (MyD88) or Toll/interleukin-1 receptor domain-containing adapter inducing IFN-β (TRIF)
The compensatory model that is mediated by the Wnt signaling pathway and p53 in mESCs
Activation of an RTK induces dimerization and downstream phosphorylation of non-receptor tyrosine kinases
A schematic overview of the Aβ-Cav1.2-ptau-autophagy pathway
IGFBPs determine the IGF-I accessibility to its receptor through IGF-I binding, while IGFBPs may also possess IGF-I binding independent action
Metabolic map of the propionate pathway and erythromycin biosynthetic pathway
Typical antidepressants, such as SSRIs, block monoamine reuptake by the 5-HT transporter (SERT)
BDNF binding to the extracellular domain of TrkB induces dimerization and activation of the intracellular tyrosine kinase domain []
Signaling pathways of the fibroblast growth factor receptor in neural stem cells
a | Structure of the Drosophila melanogaster testis
In the absence of Wnt (left), cytosolic β-catenin is continually phosphorylated by casein kinase 1α (CK1α) and glycogen synthase kinase 3β (GSK-3β) within an Axin1 scaffold complex
Model for possible mechanisms of regulation of DP thymocytes by multiple factors
a, Most normal healthy cells outside the brain are not affected by 2DG-ABT combination
The recapitulation of heart development can provide useful insight for optimizing differentiation protocols
Until recently, the exact mechanism of 5-aza induced cardiomyogenesis was largely unknown and attributed to demethylation, and subsequent activation, of an unknown cardiac-related gene
Membrane-bound Notch ligands (Dll1,3,4 and Jag1,2) are characterized by a Delta/Serrate/Lag2 (DSL) motif (yellow) located in the extracellular domain
Toll-like Receptors (TLRs) recognize specialized structural motifs on the microbes known as pathogen-associated molecular patterns (PAMPs)
The proposed mechanisms of interaction between TLRs and MUCs: I
Simplified signaling pathway of the effects of resveratrol involved in metabolic control in the skeletal muscle
The effects of resveratrol on a simplified signaling pathway involved in metabolic control in the liver
Generally, a given cell type forms only one or two of these products in abundance
Schematic illustrating the Wnt/β-catenin pathway
Common mechanisms by which the Wnt/β-catenin pathway is dysregulated in cancer
Additional mechanisms by which Wnt/β-catenin signaling can be modulated in cancer
Schematic illustrating numerous small molecules and biological compounds identified in the literature that inhibit Wnt/β-catenin signaling at various points in the pathway
Phytoestrogens-induced NO release from endothelial cells
Effects of phytoestrogens on ECs and VSMCs
Multiple messengers contribute to NMDAR-induced metaplasticity
Pathway of formation and catabolism of HDL particles
(A) Ligand-independent EphA2 signalling. Activated AKT can phosphorylate... (B) Ephrin-A1-induced EphA2 signalling. Upon ephrin-A1 ligation of EphA2...
Signaling pathways involved in the action of A3AR agonists
EGFRvIII represses the Erk pathway and preferentially activates the PI3K/Akt pathway, thereby achieving optimal cell growth
EGFR can specifically bind with EGF, TGF-Œ±, AR, BTC and EPR ligands
M.tb-derived ligands (LAM, 19 kDa protein, heat shock proteins 65 and 71, and M.tb DNA) bind to TLR2, 4 and 9 and recruit adaptor protein MyD88 (myloid differentiation primary protein 88) to the TLR receptor complex, which associates with IRAK1 and 4 (IL-1R-associated kinase).
Sympathetic nervous system (SNS) fight-or-flight stress responses deliver epinephrine (E) and norepinephrine (NE) into the tumor microenvironment via circulating blood and NE release from local sympathetic nerve fibers
Ingenuity Pathway Analysis of genes that are differentially methylated (P<1.8 × 10−6) between normal mucosa of cancer patients and controls
Regulation of insulin sensitivity by electrophiles through adduction and inhibition of PTP1B
O-linked N-acetylglucosamine (O-GlcNAc) is a nutrient sensor and underlies glucose toxicity
Insulin activates the insulin receptor tyrosine kinase which subsequently tyrosine phosphorylates IRS1
Insulin activates the insulin receptor tyrosine kinase which subsequently tyrosine phosphorylates IRS1 and 2
Binding of TSP1 to CD47 has a global effect upon the canonical NO pathway
Corresponding components in Drosophila and mammals are shown in the same color
Model of the Sema3A-activated signaling pathway that triggers adhesion site disassembly
The calcineurin activity rhythm is driven by the circadian oscillator in photoreceptors
IL-1 signaling leads to actin stress fiber formation
BTB restructuring and spermiation are coordinated by IL-1Œ± during spermatogenesis
For Wnt signaling, the transcriptional coactivator, β-catenin, is degraded in the absence of a Wnt signal, whereas the scaffold protein, Axin, is stable
(A) In the absence of Wnt signaling and in the presence of inhibitors su... (B) Wnt signaling is activated by binding of the Wnt ligand to its recep...
Calcium signalling pathways during dorso-ventral specification in Xenopus laevis and zebrafish.Wnt regulated calcium signals promote ventral cell fates via G-protein transduction mechanisms and act through CaM kinaseII and calcineurin to upregulate ventral transcription factors and downregulate dorsal transcription factors; this pathway also downregulates dishevelled signalling via PKCβ, thus antagonizing the canonical dorsalizing Wnt pathway and stabilizing β-catenin ventrally
Proposed mechanism underlying FGF-mediated inhibition of RhoA after ICH
Model for the potential role of altered cytokine-mediated signal transduction and mitochondrial metabolism in DPI- and DTI-related growth control
Numerous TLRs are expressed and activated in astrocytes including TLRs 2, 3, 4, 5, 7, and 9
Potential integration of mitochondrial oxidative and antioxidant pathways by PGC-1Œ±
A potential role for PRC in orchestrating a balance between cell cycle entry and the inflammatory response to metabolic stress
This schema shows the interconnected network of the key metabolic and signaling pathways, including glycolysis, oxidative phosphorylation, the pentose phosphate pathway, and critical cell signaling pathways
The KIT/KITLG pathway in primordial and small primary follicles participates in oocyte viability and survival
A schematic model for the Nedd8-mediated activation of the DNA damage-inducible FANCD2 monoubiquitination
Many human cancers including breast cancer possess an enhanced tumor-initiating capacity, can undergo self-renewal, partially recreate the cellular heterogeneity of the parental tumor, and seem to be generally more resistant than other cancer cells to conventional anticancer therapeutics
Unconventional roles of kinesins in cell signaling
miRNAs that promote or inhibit tumorigenesis provide diverse functions within oncogenic and tumor suppressor signaling pathways
Elevated expression of mutated / overexpressed oncoproteins activates HSF1 and leads to elevated HSP expression in mammary carcinomata
A schematic representation of mammalian target of rapamycin (mTOR) signaling pathway for the regulation of skeletal muscle protein synthesis in response to growth factors, nutrition, and mechanical stimuli
(A) A diagrammatic description of the developmental defect in nephrogenesis caused by genetic deletions or by treatment of cultured nephrons with signaling pathway modulators
Spinal cord-induced MM was treated with PKA pathway signaling modulators and observed for defects in tubule morphogenesis
MAPK signalling pathway and PI3K/IP3signalling pathway in C
(A), In a two-state view of GPCR activity, where the receptor displays only a single active state, the decision of which G protein to couple to or whether to choose a G protein-independent pathway via arrestin binding must be determined by the number of receptor molecules that achieve the active state (i.e., strength of signal).
(A) In proliferating cells under normoxic conditions, citrate is synthes... (B) In cells proliferating in hypoxia and/or with HIF-1 activation, gluc...
Regulation of cancer stem cells by inflammatory cytokine networks
Rac is activated by tyrosine-kinase receptors (RTKs), GPCRs, integrins and stress
The cellular response to DNA damage is initiated by proteins that sense the damage and signal to mediator proteins
The principal protein-protein interactions that regulate hTERT involve cross-regulation between hTERT and the cell cycle, carried out largely by cyclin/cdk complexes and transcription factors that bind to the hTERT promoter
Commonly mutated pathways in glioblastoma
A. The UPR is an adaptive signaling pathway where the proximal activators of each of its three arms (PERK, ATF6, IRE1α) are normally activated following their dissociation from HSPA5 (GRP78; BiP).
The tick creates a feeding pit with its mouthparts, using its hypostome (a barbed protuberance) as an anchor to the skin of its host
Signals elicted by the TGF-β pathway involve two cell-surface receptors at the brain microvascular endothelium, which are designated ALK1 and ALK5
Inhibition of BRAF prevents proteasomal degradation of FOXO3a and BIM by blocking MEK/ERK mediated phosphorylation of FOXO3a at Ser294, Ser344 and Ser425 as well as phosphorylation of BIM at Ser69
Multiple acquired (shown in green) and intrinsic (shown in pink) mechanisms of BRAF inhibitor resistance have been identified
The d-mannose/l-galactose pathway (7) is in black, the proposed l-gulose pathway (20) is in grey
Pathway Analysis of Gene Array Data from CWR22RV1 xenografts treated with PD325901 for three weeks
The cellular prion protein (PrP) consists of 3 α-helical domains and a highly disordered but functionally conserved N-terminal domain that interacts with a number of key regulatory proteins of several pathways to promote cell survival and proliferation
A schematic model depicting activation of the AIM2 inflammasome by F
The mechanism depicted is based on work with the mouse mammary gland as an experimental model
The pheromone response pathway in Cryptococcus neoformans
The primary therapeutic targets in the Ras downstream signaling pathway
APE1 role in DNA base excision repair (BER)
Apart from diffusion, the transport of free fatty acids (FA) across the brush border membrane (BBM) is facilitated by different proteins, such as plasma membrane fatty acid binding protein (FABPpm), fatty acid transport protein 4 (FATP4), and fatty acid translocase (FAT/CD36)
Insulin, IGF-I and IGF-II binding to IR and IGF-IR
Coenzyme Q10biosynthetic pathway and electron transport role in the mitochondrial respiratory chain
PI3K/Akt pathway impairment is a key feature of IR and vascular dysfunction
(a) The β-amyloid precursor protein (APP) under... (b) APP is also subjected in neurons to a non-a... (c) The relative abundance or absence of the li...
Proposed signaling pathway for ATP release from erythrocytes in response to exposure to low O2
Common mechanisms for PLCŒµ regulation of CICR in cardiac myocytes and pancreatic β cells downstream of Gs-coupled receptors
Schematic representation of the various pathways involved in the cellular interactions of HEDS
Schematic of an adipocyte cell with large red lipid droplets, indicating that overexpressed GPS2 binds to TRAF2 and Ubc13 at the level of the TNFR1 membrane complex and inhibits their enzymatic activity
Schematic model depicting the proposed signaling pathway in LH/hCG-induced LHR mRNA down-regulation.Binding of ligand to LH receptor induces activation of ERK1/2 through the cAMP/PKA pathway
Arterial-venous and lymphatic specification in vertebrate embryo
CCM3 interacts with multiple signaling complexes
Schematic diagram illustrating the proposed interaction between CDH17 and Wnt/β-catenin pathway during HCC progression
Wnt signals in two different ways depending upon the activation (canonical) or the non-activation (non canonical) of β-catenin
Glucose, fatty acid (FA) and glutamine metabolic pathways
Top panel: In normal and during cholestatic injury, histamine receptors are found in small and large cholangiocyte populations
TGFβ signaling pathway and its integration with other major pathways that is likely to be involved in the pathogenesis of cardiovascular diseases in elderly patients
(A) The key signaling nodes that regulate mTORC1 and mTORC2
Schematic model for inhibition of cell proliferation by EGCG analogs
Upon synthesis in the endoplasmic reticulum and glycosylation in the Golgi, CLN3 has several potential fates that may in part be mediated by compartment-specific interacting proteins
Tbx1 regulates cell proliferation in the cervical loop either by activating the Fgf signaling pathway or by attenuating PITX2 activation of p21 expression
The signaling and inhibitions of STAT3 are shown, with areas of special emphasis for the dominant negative mutants shown
Acute phase response pathway is shown, with differentially expressed genes (FDR ≤ 15pct; difference ≥ 10pct) indicated in red (down-regulated) or in green (up-regulated)
Nrf2-mediated oxidative stress response pathway is shown, with differentially expressed genes (FDR ≤ 15pct; difference ≥ 10pct) indicated in red (down-regulated) or in green (up-regulated)
Signaling pathways are depicted schematically
(A) Analysis of metabolism is similar in principle to the analysis of traffic patterns, with many of the same uncertainties
ABCA1 null macrophages have an enhanced pro-inflammatory response to ligands for TLR2, TLR4, TLR7, and TLR9 compared with wt macrophages, likely reflecting increased cholesterol and TLR assembly in lipid rafts
(A) Western blot showing pan-histone 3 acetylation (H3ac) levels in HCT1... (B) A model of how glucose increases histone acetylation. First, it cont...
The Wnt/Ctnnb1 signaling pathway is involved in self-renewal of leukemic stem cells
(a) Treatment with PAR... (b) DNA DSBs can be re... (c) 5′ – 3′ exonucleas... (d) Ku70/80 can potent... (e) Treatment with cis... (f) Interstrand cross-...
Proposed model outlining the role of PPARŒ¥ in the modulation of the radiation-induced proinflammatory response in BV-2 cells
Following TCR engagement, a critical event is the activation of PLCγ following the orchestrated action of proximal tyrosine kinases and adaptor molecules
TLR signaling is mediated by the MyD88-dependent and TRIF-dependent pathway
A schematic model for mechanical force-induced glomerular podocyte apoptosis
A. The MYC protooncogene is depicted downstream of receptor signal transduction pathways, which elicit positive or negative regulation of the MYC gene.
During strong postysnaptic depolarization, which is mediated by AMPA receptors (AMPA-R), calcium (Ca2+) entry through NMDA receptors (NMDA-R) and voltage-gated calcium channels (VGCC) initiates synaptic plasticity
The cell signaling pathways involved in ischemic postconditioning
The figure illustrates the steps in the processing of miRNA, also summarized in the text
Following exposure to DNA damaging agents, the DDR signaling cascade is activated by sensor proteins such as MRN
Schematic representation of the cAMP response element binding protein (CREB)-CCAAT enhancer binding protein (C/EBP) pathway activated during memory formation
Target-derived NGF mediates axon growth and synapse assembly in sympathetic neurons via endocytic signaling mechanisms
Post-Translational Regulation of β-Catenin Protein by Notch.Notch can negatively regulate active β-catenin levels in a non-canonical fashion
The IIS, TORC1, and TORC2 pathways are involved in growth (see text)
Leukocyte recruitment to sites of injury/infection: dominant role of ROS
Role of Rac1/RhoA balance in endothelial barrier integrity: impact of ROS and NO
Cooperative role of ROS and NO in angiogenesis
Metabolic pathway for disulfiram in humans
Glucose entering the cell is immediately phosphorylated by Hexokinase 2 (HK2), producing glucose-6-phosphate (G6P)
PI3K/Akt-mediated phosphorylation results in the inactivation of FoxO transcription factors
Examples of ciliary chemo-, photo-, and mechanotransduction
Proposed mechanism for fatty acid-mediated modulation of endothelial cell activation induced by TNFŒ±
Dmrt genes integrate sex-specific, spatial, and temporal cues to induce sexually dimorphic differentiation in restricted groups of cells
The pioneer-round of translation utilizes newly synthesized mRNA bound by the cap-binding protein heterodimer CBP80-CBP20 (CBC) and, provided the mRNA derived from splicing, at least one exon-junction complex (EJC, which consists of but is not limited to MAGOH, Y14, PYM and eIF4AIII) situated ~ 20–24-nucleotides upstream of such a junction
On the left panel is a model depicting crosstalk between the PI3K/AKT pathway and the androgen receptor (AR) signaling pathway with each pathway negatively regulating the other
Transcriptional changes in TGF-β1 signaling pathway
Adenovirus VA RNA inhibition of both the Interferon/PKR pathway
A model of the signaling pathways regulating radiation-induced bystander effects through expression and secretion of soluble biologically active factors
CTGF Signaling in ChondrocytesCTGF interacts with (an) unknown receptor(s) on the surface of chondrocytes via binding of one or more of its four distinct modules
Regulation of CTGF Expression by TGF-β1 in OsteoblastsTGF-β1 induction of CTGF in osteoblasts requires Src, Smad and ERK signaling
Scaffolds can organize pleiotropic kinases into stimulus-specific signaling modules to direct them to one specific pathway
Shown is a simplified model of how aberrant IFNŒ± production can occur in SLE patients
Proposed metabolic pathway of B[a]P-7,8-dione in three human lung cells
A proposed disease pathway in arrhythmogenic cardiomyopathy showing potential mechanisms of gap junction remodeling
PPARŒ± signaling canonical pathway in chronic arsenic-exposed lung epithelial cells
Ced-1 may coordinate multiple mechanisms to link innate immunity to the Unfolded Protein Response
Models of iron metabolism in the enterocyte, hepatocyte, macrophage and erythroid precursor are shown with labels indicating those gene products for which models of deficiency have been recently reported
Schematic of depiction of arachidonic acid signaling pathway highlighting genes measured in this study
Here we present a schematic of the immunosuppressive pathways throughout the brain tumor and molecular inhibitors that reverse the potent immunosuppression
Many host factors are involved at each step of the HCV life cycle, which starts with virus binding to its specific receptors (CD81, CLDN1, OCLN, and SR-BI)
Role of the TSH receptor in the immunopathogenesis of Graves’ ophthalmopathy
Depiction of Notch pathway and loci at which current and experiemental inhibitors block
The hexosamine biosynthetic pathway and its dependent processes
Components and targets of pro-phenol oxidase, Toll-Dorsal/Dif and JAK/STAT pathways
Many transcription factors and molecules downstream of TCR control CD127 expression, either by inducing or inhibiting its transcription
The RAS proto-oncogene family (KRAS, HRAS, NRAS and RRAS) encode four highly homologous 21kDa membrane-bound proteins involved in signal transduction
Downstream targets of AKT are involved in cell growth, angiogenesis, cell metabolism, protein synthesis, and suppression of apoptosis directly or via the activation of mTOR
Regulation of p53 can occur through the MDM2 oncogene which reduces p53 levels through degradation by ubiquitination
Notch, Wnt, and Hedgehog (Hh) are stem cell self-renewal pathways that are often deregulated and aberrantly activated in lung cancer, thus representing key therapeutic targets
Regulation of vascular cell signaling by thrombospondin-1 and CD47
Assembly of targeting patches and inside–out orientation of the secretory pathway
SHP-1 and SHP-2 are phosphatases that can play opposite roles in the regulation of signalling pathways
A schematic representation of sites of PP2A activity within the network of ERK activation
NSAIDs perturbed genes related to thrombosis, fibrinolysis, and PAR signaling
Simplified model of the opposing roles of PHB1 in tumorigenesis
Main interaction sites of anticancer metal complexes with cellular redox and oxidative stress pathways
A simplified scheme of the correlation between Notch signaling components and CDX2 amounts determined in the study with and without inhibition by DCA and DAPT
Diagram of genes that have been implicated in susceptibility to CL and ML disease caused by L
The central role of β-catenin in Wnt signaling and the cadherin complex
Intersection of pathways controlling Wnt/β-catenin signaling and cadherin-mediated adhesion
The Rasopathy disorder associated with each gene is indicated in red
Mechanisms of action of TIEG in the TGFβ-Smad signaling pathway
Ras signaling pathway is highlighted in Red
There are three major models for the crosstalk between endocytosis and cell signalling
The mutations in glutamate signaling pathway and its associated proteins in melanoma
EphA2 signaling in normal epithelial cells and tumor cells
Environmental regulation of GSC proliferation at developmental stages of the gonad
miR-23a primarily increases cell motility through down-regulation of its target MTSS1 and up-regulation of the SRC signaling pathway, while miR-27a promotes cell proliferation in part via inhibition of FBXW7, leading to the up-regulation of FBXW7 ubiquitin substrates including Myc, Jun, and Notch
Function network built upon genes selected from the identified genetic component
mTOR signaling and its regulation by DGKs
ARE: Antioxidant response element; DUOX: Dual oxidase; H2O2: Hydrogen peroxide; NO: Nitric oxide; NOS: Nitric oxide synthase; O2: Superoxide radical; ONOO‚àí: Peroxynitrite
Recognition of pro-inflammatory stimuli, presence of microbial cell wall components, secreted TNFŒ± or various other cytokines, through their respective receptors triggers a pro-inflammatory first response of the IEC
Recent evidence suggests that ASC has an inflammasome-independent role in the activation of MAP kinase and NF-Œ∫B signaling, which leads to the transcriptional activation of a panel of cytokines and chemokines
Oncogenic signaling pathways regulated by NO and PP2A
(A). Engagement of HVEM by membrane LIGHT during T-T cell interactions l... (B). Engagement of BTLA on T cells by HVEM expressed in antigen-presenti...
Identification of genes in the camp-mediated signaling pathway whose expression was altered in association with recovery
The canonical pathway of alternative macrophage activation involves activation of STAT6 by the Th2 cytokines IL-4 and -13
Signaling pathways and their targeted therapies in NSCLC
LPS/ KLA stimulated eicosanoid metabolism and signaling pathway
a. SnoN promotes TGFβ-induced transcription and biological responses by acting as an adaptor inducing a Smad-SnoN-ING2 multiprotein complex on promoters of TGFβ-responsive genes.
HCMV management of the PI3K/AKT/mTOR pathway
A schematic model of the Hippo signaling cascade in mammals
A schematic representation of androgens up-regulating PCa cell proliferation via p66Shc-ROS signal pathway
FOXO proteins are involved in multiple signaling pathways that control cell proliferation, apoptosis, survival, and immune functions in response to external and internal stimuli
Schematic representation of the signalling transduction pathways involving the tuberous sclerosis proteins, hamartin and tuberin
Potential targets for inhibition within the EGFR signaling pathway
This is an example of the DBN model trained with experimental and control expression data showing the mechanistic genes indicated by concentric rings around the node (each node represents a gene and its expression levels)
(A) Under conditions where PTEN is present, Akt is activated predominant... B) p110β may also function in a PIP3-independent manner such that its ca...
The mTORC1 complex regulates the activity of downstream targets that eventually lead to enhanced translation
The Ras/Raf/MEK/ERK pathway.Binding of growth factors (GF) to receptor tyrosine kinases (RTK) leads to recruitment of adaptor proteins and guanine exchange factors (GEF)
The family of surface-receptor tyrosine kinases encoded by EGFR consists of four members that form homodimers or heterodimers after ligand binding
The mTOR kinase nucleates two characterized protein complexes termed mTORC1 and mTORC2
mTORC1 promotes translation (A) and inhibits autophagy (B), by integrating nutrient signals generated by amino acids (C), growth factor signals relayed by the insulin and insulin-like growth factors (D), energy signals acting through AMP-activated kinase (AMPK) (E) and various stressors including hypoxia (F) and DNA damage (G)
Three major apoptotic pathways, initiated by the apical caspase-2, −9, and −8/10, are depicted
Neuroprotective signaling pathways employed by Erythropoietin
Proteome coverage of the KEGG ‘Insulin Signaling’ pathway
A) Wnt family members initiate sig... B) The GPCR-like LGR5 and 6 are ex... C) The release of the neurotransmi... D) Notch signaling is dispensable...
Transcription factors and signaling involved in the osteoblast differentiation pathway
Seven important signaling networks of osteoblast differentiation
Please refer to text for specific details
The association between mTOR and the PI-3K–Akt intracellular signaling pathway in vascular endothelial cells
As glucose enters the glycolytic pathway, a minor portion is branched to hexosamine biosynthetic pathway to produce GlcNAc which can be used as substrate for histone GlcNAcylation by OGT
a) In the absence of Wnt signals, the destruction complex Adenomatous Po... b) Upon Wnt binding to its Frizzled (Fzd) receptor and Lipoprotein Recep...
The upper level of the diagram depicts signaling molecules at the cell surface, while the lower level depicts resulting changes in gene-transcription and apoptosis-related pathways
Interaction of pathogen recognition and ST2 receptor systems with FcŒµRI leads to substantial enhancement of production of cytokines and chemokines
Anaplasma phagocytophilum infection of human cells causes IL-8 secretion, which leads to the recruitment of neutrophils
Proposed scheme for the inhibition of both arms of the mTOR pathway by p-XSC and rapamycin in C4-2 cells
A illustrated the interaction of the genomic and acute estrogen signaling pathways in regulating nitric oxide (NO) signaling
Key branches of the insulin signaling cascade
A simplified overview of major signaling pathways known to control salivary gland development based on experimental studies
Cardioprotection is typically initiated by activation of G-protein coupled receptors, which result in activation of the PI3K signaling pathway
After hepatic uptake through OCT1, the mitochondria is the primary target of metformin which exerts specific and AMPK-independent inhibition of respiratory-chain complex 1
Intrinsic cell death pathway that occurs as a result of Bax-like proteins mediated damage to the mitochondrial membrane
Interactions between cytokine and glucocorticoid receptor (GR) signaling pathways
HIF regulation and mTOR pathway connections
Potential mechanisms involved in hypoxia-induced systemic hypertension
Summary of the various phosphorylated residues on eEF-2K
Mesenchymal stem cells (MSCs) may have both growth inhibitory and stimulatory effects on tumours
Synergy of chemotherapy and radiotherapy with mesenchymal stem cell (MSC)-delivered anticancer agents
This is a schematic depicting a selection of factors involved in the DDR that are phosphorylated in response to DSBs
Upon entry into G1, cyclin D/cdk4 and cyclin D/cdk6 complexes phosphorylate the retinoblastoma protein (Rb), allowing release of transcription factor E2F family members
The study of lymphocyte activation requires observation of samples that vary in size over six orders of magnitude
A model for TLR-induced corneal inflammation
A) Exposure to MDP liberates NOD2 from its autoinhibited state allowing... B) TRAF4 inhibits NOD2 signaling in a manner dependent on NOD2 binding a...
Proposed regulatory mechanism of ERβ in colitis-associated colon cancer
HIV-1 Nef promotes viral replication and viral survival by hijacking host cell machinery to achieve immune evasion and anti-apoptosis
IL-2 signals by activating three principal signaling pathways, the SHC/RAS/MAP kinase pathway, JAK1/JAK3/STAT5 pathway, and PI 3-K/AKT/p70 S6 kinase pathway
(i). PV decreases peroxisome proliferator–activated receptor γ (PPARγ) activity by competition with PPARγ for binding to PPARγ response elements (PPRE) as heterodimers with PPARγ or the retinoid X receptor (RXR).
Filled symbols are 13C, open symbols are 12C
(A) Schematic representation of the Hippo pathway evolution
Signaling loops initiated by TGF-β accelerate downstream action and effects via miRNAs
Initiation of the TGF-β signaling cascade occurs upon ligand binding to TβRII and subsequent TβRI-TβRII hetero-tetrameric complex formation, and TβRI is activated through phosphorylated in the cytoplasmic GS domain
Under unstimulated condition, TAK1 associates with TβRI through complex formation with TAB2 and TRAF6
TGF-β1-induced TAK1 activation triggers downstream signaling pathways such as the MKK4-JNK, or the MKK3-p38 cascade, and promotes degradation of Ik-B, which in turn lead to the activation of transcription factors ATF-2, AP-1 and NF-kB, respectively, to regulate the expression of extracellular matrix proteins, including collagens and fibronectin, and inflammatory cytokines
TAK1 activation of MKK3-p38 induces the expression of LC3, whereas JNK activation induces the expression and activation of Beclin 1
Cell adhesion molecules pathway (immune system) containing genes differentially regulated by Tannerella forsythia in calvarial bone and soft tissue compared with sham-infected controls at P ‚â§ 0.05, adapted from PATHWAY EXPRESS and using the Kyoto Encyclopedia of Genes and Genomes nomenclature
Focal adhesion pathway containing genes differentially regulated by Tannerella forsythia in calvarial bone compared with sham-infected controls at P ‚â§ 0.05, adapted from PATHWAY EXPRESS and using the Kyoto Encyclopedia of Genes and Genomes nomenclature
A. In the early stage of HIV-infection, the binding of HIV-1 or HIV-1 proteins with macrophage cell surface receptors induces intracellular signaling cascades such as Akt-1, ERKs, and NF-Œ∫B pathways.
Schematic representation of the interleukin (IL)-12/IL-23/interferon (IFN)-γ pathway and its role in mycobacterial disease control
Cardiac myocyte signaling coupled to phosphodiesterase (PDE) 5
Wnt/β-catenin, AKT, TGF-β and IL-6/STAT3 signaling pathways are deregulated in hepatic CSCs
KEGG pathway of the renin-angiotensin system
[LM5]Strategies for treatment of traumatic central nervous system (CNS) injuries
Schematic diagram of the Ras signaling pathway which is disrupted in juvenile myelomonocytic leukemia (JMML)
A schematic of calcium signaling pathways in osteocytes investigated in present study
The schematic depicts regulatory some of connections within the Hippo pathway, and between Hippo signaling and other pathways discussed in the text
A schematic model showing the existence of distinct secretory pathways in pheochromocytoma
Identification of multiple disrupted components in a biological pathway
Schematic displays hypothesized pre- and post-synaptic signaling pathways activated by IL-1β to induce synapse loss
Long-term repopulating hematopoietic progenitors (LSK-flt3‚àí) progress through LSK-flt3+ progenitors which branch into myeloid (MP) and lymphoid (LP) progenitors
By combining the highlighted functions and pathways from the Ingenuity analysis of the hMitChip3 cDNA microarray results and known pathway data, the effects on the energy metabolism pathways in UOK268 were modeled
Simplified diagram depicting Ras signaling and crosstalk with PI3 kinase- Akt pathway in leukemia
Model of molecular mechanisms underlying PA and histologically anaplastic PA
Proposed pathway of SubAB-induced apoptosis
Oxidative stress may reduce UPP activity in RPE
Proposed role of ER calcium underlying early disruptions in synaptic homeostasis at the CA3–CA1 synapse in AD
Postulated interactions between 20-HETE and RAS in the vascular endothelium
The figure shows a summary of the normal pathway of heme biosynthesis, with emphasis on uroporphyrinogen decarboxylase [UROD] and its inhibition by an oxidation product thought to be derived from uroporphyrinogen
A. The most significant network from Ingenuity Pathway Analysis for upregulated proteins in the conditioned media shows evidence of TGFβ-1 regulation.
Insulin signaling activates the mTOR pathway via Akt and thus suppresses autophagy
12-LOX generates 12(S)-HETE by its enzymatic activity on cell membrane arachidonic acid
Schematic representation of the expression and role of cyclic nucleotide signalling pathway in control of electrical activity in pituitary cells
Proposed mechanisms leading to VEGF signaling pathway inhibitor-induced hypertension
In addition to the previously described autoregulatory loops between Fgf, Wnt and T-box genes (grey arrows), we find evidence of more direct intertwining of the Fgf and Wnt pathways (colored arrows)
Biological targets under investigation for treatment of SLE
Trafficking of DSL ligands and the Notch receptor to and from the plasma membrane of both signal sending cells and signal-receiving cells control activation of the pathway
In normal physiological situations, the PI3K pathway is activated by an extracellular stimulus that results in activation of a receptor tyrosine kinase (RTK)
The activity of Wnt canonical signaling pathway in the normal and tumor cells
The activity of PI3K signaling pathway in normal and tumor cells
Chondroitin sulfate proteoglycan 4 (CSPG4) Signaling Pathways
The model depicts most identified components of the Drosophila Hpo pathway, grouped into modules as discussed in the text
Upon disassembly of the cytoplasmic cell-adhesion complex, catenins are released and accumulate in the cytoplasm
Termination steps during IgE-mediated activation
Aβ oligomers stimulate oxidative/nitrosative pathways involving NMDA receptor, nNOS and NADPH oxidase leading to production of ROS and activation of cPLA2
(a) Insulin and IGF1 receptors activate IRS proteins, which in turn acti... (b) The generic primary structure of Akt proteins is shown. Binding of P...
A. The signaling pathway from Insulin/IGF1 receptor through IRS, PI3K, and Akt in mammalian cells.
Interface between hemostasis and adaptive immunity
Signaling pathways for estrogen production and action
Metabolic flux through the purine salvage pathway in L
In step 1, human papillomavirus (HPV)-E6 protein promotes p53 degradation
Growth factors stimulate the MAPK and insulin signaling pathways, leading to TSC2 phosphorylation and inactivation
A. In AdV-infected macrophages STAT1 activation, IFNβ production and MxA mRNA levels were enhanced.
The intersection of a MAPK signaling pathway and Rho-GTPase cycling is illustrated along with the effector proteins from bacteria that target these pathways
Resveratrol inhibits PDE activity and induces cAMP signaling via Epac1, which activates PLCŒµ, resulting in Ca2+ release via the Ryr2 Ca2+ channel and, ultimately, the activation of the CamKKβ-AMPK pathway
Current model of HIV-1 neuropathology and potential sites for therapeutic intervention (protective factors are shown in italic): Immune-activated and HIV-infected, brain-infiltrating macrophages (Mphi) and microglia release potentially neurotoxic substances
Proposed model for mitohormesis in response to reduced insulin/IGF1-signaling.A
Transmembrane CLRs involved in antifungal immunity and their intracellular signaling pathways
Involvement of the target of rapamycin (mTOR) pathway in human disease syndromes
Sixty-one genes reported in the relationship with cancer are represented from all identified phosphoproteins in LNCaP cells
Reciprocal interactions between RGS10 and PKA promote DA neuron survival by potentiating CREB signaling and attenuating caspase-dependent apoptotic cascades downstream of TNF receptor activation
Age-related alterations in receptors and signaling molecules of CD8 T cells
Regulation of mammalian target of rapamycin complex (mTORC) signaling networks
HIF target genes encode proteins involved in critical aspects of cancer progression
The extrinsic or death receptor-mediated pathway is mediated by sequential engagement of specific ligands such as FasL, TNF-α, TRAIL, and TWEAK with cognate receptors, formation of the death-inducing signaling complex, and activation of initiator caspases 8 and/or 10
Major pathways for maintaining intracellular GSH balance include de novo synthesis, regeneration from GSSG, and extracellular GSH uptake
(A) Innate-like B cells, that is B-1 and margin... (B) Subsequently, B-1 and marginal zone B cells... (C) Recent data demonstrate the direct involvem...
Working network obtained according to Ingenuity data base (www.Ingenuity.com) as indicated in Methods.
Illustration of the metabolic pathway analysis for zidovudine with thick arrows indicating targets identified by the automatic classifier
TAP-MS PPI RTK-Ras-ERK signaling network
The P2Y2R modulates a variety of cellular processes through classical G protein-coupled receptor pathways and unique receptor motifs
P. gingivalis interacts with Toll-like receptor (TLR)-2 (as part of a CD14–TLR2–TLR1 signaling complex) and with TLR4.
Model showing a role for Yap in governing cardiac growth and survival by interlinking the Hippo, IGF, and Wnt pathways
The progesterone regulated paracrine signaling model depicted within the uterine compartments at the time of embryo implantation
Bone regeneration or bone remodeling involves bone resorption by osteoclasts (OC) and the following bone formation by osteoblasts (OB) within basic multicellular units (BMU)
Model for the role of Wnt signaling in hypothalamic progenitor differentiation
Possible cellular responses and transcriptional regulation initiated by activation of opioid receptor signaling
Proposed model for the involvement of NF-Œ∫B signaling in opioid receptor-expressing immune and neuronal cells
Putative microRNAs identified to regulate gene expression in the PGE2pathway
(A) AMPK in cancer. Upon cellular stress, the a... (B) AMPK in type 2 diabetes. High glucose level... (C) AMPK in cardiovascular disease. Cardiac hyp...
A, in hormone-dependent ER+ breast cancer cells, estrogen (E2) activates ER-mediated transcription (genomic pathway) and nongenomic ER-mediated signaling
The choreography of Ca2+signaling and examples of virus-induced perturbations on Ca2+ homeostasis
Schematic of ATM signaling upon oxidative stress and double-strand DNA breaks
Schematic respresentation of anterograde and retrograde trafficking pathways for KCa2.x (left) and KCa3.1 (right) channels
The major signaling pathway causing insulin resistance is the convergence of multiple stimuli leading to the activation of S6 kinase
Schematic representation of the MAPK cascade activation and potential cross talk signals
NAD+ is the primary neurotransmitter mediating purinergic inhibitory regulation of colon motility (, )
Network analyses of synaptic plasma membrane (SPM) proteins down-regulated in the DHA-deficient mouse brain
Schematic representation of the zonulin mechanism of action
HER2 overexpression confers oncogenic addiction to NFŒ∫B-mediated signaling pathway
Previous studies have shown that in PC2-defective cholangiocytes, [Ca2+] is decreased in the cytosol and in the Endoplasmic Reticulum (ER) and store operated Ca2+ entry is inhibited, leading to adenyl cyclase 6 (AC6) activation and inappropriate overproduction of cAMP
Schematic of innate immune signaling triggered by WNV infection through cytosolic RLRs or endosomal TLRs
Network analysis suggests an immune response and inflammation in ulcerative tissue and non-ulcerative tissue of patients with ulcerative interstitial cystitis (IC)
Lineage commitment of PrE and EPI cells is thought to occur around the 64-cell stage and is driven by a core-regulatory network of lineage-restricted transcription factors
Following recognition of a microbe, or unknown Plasmodium ligand, by soluble PGRP molecules, the Toll pathway is stimulated by binding of the ligand Spätzle with the Toll transmembrane receptor
Schematic representation of the signaling pathways involved in T-cell activation
The intact Fas–FasL-mediated apoptosis pathway is shown
STATs serve as the converging point for many signaling pathways that are mediated through cytokine receptors, growth factor receptors and nonreceptor tyrosine kinases, which are commonly activated in cancer cells
Aberrant activation of the MAPK signaling pathway in papillary thyroid tumor cells
(A) Experimental approach: HepG2 cells were pre... (B) PKN pathway map (derived from the Ingenuity... (C) Summary of the compressed model networks wi...
Network analysis of proteins found to be significantly altered in abundance in the CSF proteome by ANOVA (p value <0.05) following analysis of individual subject samples
(A) Summary of the regulation of phase II and anti-oxidative genes via t... (B) A simplified putative model for crosstalk between Nrf2 and NfkB in i...
P. gingivalis has surface structures that interact with Toll-like receptor (TLR)-2 (specifically with the CD14–TLR2–TLR1 signaling complex) and with TLR4.
Alveolar epithelial type II cells and alveolar macrophages likely receive cholesterol from circulating low density lipoprotein and high density lipoprotein (LDL, HDL) through the LDL receptor (LDLR) and scavenger receptor B type I (SR-BI), respectively
The proliferation/differentiation balance and sex determination in the C
Regulatory network analysis of the top genes with SNPs with p<0.001 using MetaCore’s shortest pathway algorithm (GeneGo Inc.); the nodes that are circled are the genes of interest
COUP-TFII has been reported to modulate the expression of a variety of target genes both positively and negatively
General mechanisms of resistance to trastuzumab: presence of upregulation of HER2 downstream signaling pathways
General mechanisms of resistance to trastuzumab: presence of signaling through an alternate receptor and/or pathway
The cytokine receptor is a transmembrane protein comprising an extracellular ligand binding domain (ECD), a single pass transmembrane domain (TMD), and an intracellular domain (ICD)
Schematic of mTORC1 signaling and genetic mutations at specific sites in the pathway
Nongenomic and genomic estrogen signaling pathways
mAKAPβ coordinates hypertrophic signaling leading to cardiac gene remodeling
Schematic illustrating metabolic pathways prominent in malignant cells
As a key downstream target of PI3K-mediated signaling pathway in response to extracellular stimuli such as growth factors through receptor tyrosine kinase (RTK), Akt plays an important role in regulation of diverse cellular processes
Metformin targets multiple signaling pathways to reduce the growth of cutaneous SCCs in a xenograft murine model system
Schematic representation of the Ras→Raf→MEK1/2→ERK1/2 signalling pathway
The myosin II-cortexillin I-IQGAP-kif12-INCENP control system regulates the equatorial cortex
Schematic diagrams of the role of STAT1 in antimycobacterial, antiviral and antifungal immunity
Biogenesis and functions of non-coding RNAs mediating RNAi are shown
Angiotensin II activates AT1R and AT2R in the endothelium
Stimulation of AT1R activates PKC, ERK, JNK, and p70S6K to inhibit IRS/PI3K/Akt/eNOS pathway
a | In mammalian cells, the presence of a double-stranded DNA break (DSB) is originally sensed by the MRN (MRE11–RAD50–NBS1) sensor complex
Signals from growth receptors on the cell surface are transmitted via the Ras–MAPK pathway into the nucleus, where cyclin/CDK complexes phosphorylate Rb to release E2F, causing progression of the cell cycle and promoting cellular proliferation
Growth factors or cytokines can stimulate phosphoinositide-3-kinase (PI 3-K) and the activation of Akt
Growth factors activate phosphoinositide 3 kinase (PI 3-K) and Akt
Speculative Scenario of NNK-activated β-adrenergic Signaling Suppressed by Apigenin NNK binds to the β-adrenergic receptor (β-AR) that subsequently activates focal adhesion kinase (FAK) and Src to elicit the activation of the mitogenic activated protein kinase (MAPK) pathway
Overview of Wnt signaling cascadesWnt signals can be transduced either through the canonical pathway (colored in pink) or different non-canonical pathways
Neurotrophin Regulation of Energy Balance in the Adult CNS and PNS
In the upper panels, a graphical depiction of relationships within and across conditions for a small pathway related to prostate cancer identified by a recent paper () is shown
HLA-I antibodies stimulate intracellular signals via integrin β4 in endothelial cells and smooth muscle cells in the setting of transplant atherosclerosis
Platelets secrete TGFβ1, which activates the TGFβ/Smad pathway in tumor cells
Ligand binding to cytokine-specific receptors (TNF-R2, IL-1R, IL-6R and IFNαR) located on the chromaffin cell membrane leads to the activation of multiple, potentially interacting, intracellular pathways
To confirm the activation of c-Kit signaling by KSHV, a series of kinase inhibitors were utilized
A. The PI3K/Akt axis can be activated downstream of RTK activation or as a downstream effector of activated Ras.
A schematic representation which shows possible mechanisms of action by Œ¥- and γ-tocopherol in multiple signaling pathways involved in mammary carcinogenesis
a. BBB ‘sealing’ effect and direct vasculoprotection: Beneficial cytoprotective activities of APC and its cytoprotective-selective variants involve direct effects on endothelial cells that require the cellular receptors EPCR and PAR-1 and EPCR-dependent PAR1-mediated cross-activation of sphingosine 1-phosphate receptor 1 (S1P1).
In healthy persons (Panel A), the lamina propria normally contains a diverse array of immune cells and secreted cytokines
Calcium stimulates intracellular signaling (inside–out signaling) through its binding to CaR
Distinct signaling pathways of synaptic and extrasynaptic NMDAR in neuron fate
Growth factors can activate mTOR signaling through phosphoinositide 3 kinase (PI 3-K) and Akt mediated pathways
Glucose enters glycolysis (orange panel) and is metabolized to lactate
Stem cell pathways analysis for label-retaining cancer cell (LRCC)
A hypothetical model of the role of aP2 in macrophages is depicted
In addition to cytokine neutralization (IL-1, IL-6, TNFŒ±, IL-12/23), direct cellular targeting is being used successfully in autoimmune disease
A model for synergistic cancer cell death in response to stress when TSC2, but not Pten is inactivated in the context of a deregulated Rb pathway
A) Model of the proposed function of dnlg1 in the regulation of synaptic growth and activity in the neuromuscular junction based on the analysis of loss of function and gain of function mutants
Model illustrating CD40-induced signals that mediate the expression of VEGF in endothelial cells
Estradiol membrane signaling induces spinogenesis in the ARH
Signaling pathways in regulation of gene expression, cell proliferation and differentiation
Regulation of CSCs by inflammatory cytokine networks
Epinephrine and norepinephrine enhance myocardial contractility, heart rate, and apoptosis through GŒ±s-coupled signaling pathways in heart (black arrows)
During allograft rejection, alloantibodies, inflammatory cytokines and growth factors mediate activation of the mTOR signaling pathway
A schematic representation of the crosstalk between classical and non-classical mechanisms in female reproductive behavior
Wnt transduction pathways and their functions during synapse development, function and plasticity
Wg secreted from presynaptic motor neuron endings, binds to Fz-2 and co-receptor Arrow, which are localized presynaptically and postsynaptically
At the tail region of C. elegans, the axon from the DA9 motor neuron forms neuromuscular junctions (NMJs) with the body wall muscles.
Dysregulated Wnt-FoxM1/ β-catenin signaling pathway regulates self-renewal and tumorigenecity of GSCsWnt activates its receptor Frizzled and co-receptor LRP5/6 to disrupt or functionally inactivate the destruction complex containing Axin/APC/CK1/GSK3β, leading to aberrant accumulation of β-catenin in cytosol
Several signaling pathways relevant to cancer pathogenesis have been shown to converge upon and regulate the expression and activity of PGC-1α and β, two key ERRα coactivators
Two different pathways could bypass DNA damage causing stalled replication forks
Metabolites and genes that are upregulated in induced E+R+ lung tissue vs. induced E-R+ tissue are shown in red (genes are outlined).
Serum-free medium harvested from mouse peritoneal macrophages that had been exposed to LDL (control cells) or acetyl-LDL (foam cells) was analyzed with LC-ESI-MS/MS
The hypothetical pathway links the IRF6 gene regulatory network (IRF6, TP63, TFAP2A, and TGFB3, all previously implicated in craniofacial development) with the Rho signaling pathway through ARHGAP29
A. In daf-2/InR insulin-receptor mutants, insulin-like peptides (e.g., INS-7) secreted from neurons reach intestinal cells and trigger the canonical insulin-signaling pathway, which prevents DAF-16/FOXO from entering the nucleus.
Lifespan extension via germline removal, for example by mutation of glp-1/Notch, depends on at least four signaling mechanisms: reduced TOR signaling (likely to regulate autophagy), DAF-16/FOXO regulation, increased steroid signaling via the DAF-36/DAF-9/DAF-12 pathway (which regulates various genes), and increased NHR-80/HNF-4 signaling (which enhances fatty-acid desaturation)
A) FGF23 is produced by bone cells... B) FGF23 acts at renal tubule cell... C) Osteocytes and osteoblasts are... D) FGF23 processing is carried out...
Transforming growth factor-β (TGFβ) ligand binding causes heterodimerization of type I and type II receptors
The Suggested Metabolic Pathway for 1- Methylpyrene (1-MP)
Hypothesized model for actions of the cAMP-Epac-Rap1 signaling pathway at neuronal gap junctions
IPC either directly or indirectly (via G-protein coupled receptors or growth factor receptors) activates numerous protein kinases and other cell signaling molecules, including the generation of ROS for signaling purposes
Proposed model of Cripto-1 modulation of the Wnt/β-catenin signaling pathway
Known relationships between the candidate genes
The MAP kinase pathway is activated in human tumors by the binding of ligand to receptor tyrosine kinases (RTKs), by constitutive activation of an RTK, by loss of NF1 function, or by mutations in RAS, BRAF and MEK1
The classical STAT-dependent pathway of cytokine receptor cross-talk
The alternative STAT-independent pathway of cytokine receptor cross-talk
S1P binds to S1PR1 and/or SIPR3 and activates GŒ±i
Schematic diagram of XBP-1 in the UPR Signaling Pathway
(A) Ligand traps and coreceptor molecules control the access of TGFβ family ligands to signaling receptors
(A) A TGFβ-activated Smad complex in epithelial cells represses c-MYC expression (right panel) and facilitates the induction of CDK inhibitory genes (left panel)
athways 1–3 represent genetic/epigenetic mechanisms believed to be associated with the development of sporadic colonic growths/tumors in humans and rodent models of investigation (reviewed in )
The ability of HEDS to interfere with thiol redox homeostasis and elicit loss of protein function and cell death occurs in glucose-deprived cells where HEDS detoxification is inefficient (Pathways 1–6)
The BRCA and RAD52 pathways of DNA double-strand break (DSB) repair
1α25 (OH2) D3 maybe promoting a more differentiated phenotype in cancer cells by preventing the translocation of β-catenin or its ability to form complexes with TCF4, thus decreasing mRNA levels of genes involved in cell survival and proliferation
Here we summarize the findings discussed in this review
Summary of the mechanisms of DC-mediated HIV-1 transmission to CD4+ T cells
Roles of RKIP in intracellular signaling
Putative Altered Signaling Events occurring upon treatment of GSI
Graphic illustration of the perturbation of the insulin signal transduction pathways by cellular stressors
Diagram depicting the relationship between clusterin, the intrinsic and extrinsic apoptotic cascades, and histone deacetylases
Two major signalling pathways are depicted here: the pathway involving class I phosphoinositide 3-kinase (PI3K), protein kinase B (PKB) and mammalian target of rapamycin complex 1 (mTORC1), and a cyclical mTOR-independent pathway; the basic helix–loop–helix leucine zipper transcription factor EB (TFEB)-mediated pathway is also depicted
The formation of the autophagosome depends on the initiation and/or nucleation of a specific membrane structure known as the phagophore, and on the elongation and closure of the phagophore to form a double-membrane-bound vacuole
An excitatory synapse is comprised of a presynaptic axon terminal with vesicles containing the neurotransmitter glutamate (red) that is released into the synapse in response to Ca2+ influx resulting from Na+ influx-mediated depolarization of the neuron
Wnt protein binding to seven transmembrane Frizzled receptors leads to the recruitment of Axin to the plasma membrane and phosphorylation of its co-receptor, low-density lipoprotein receptor related protein (LRP) 5/6 by casein kinase-1α (CK1α) and glycogen synthase kinase-3β (GSK3β), leading to activation of Dishevelled (Dvl) and destabilization of a β-catenin destruction complex
A schematic model depicting how HMW isoforms regulate bone formation
Simplified summary of the role of ATGL in macrophages.FFAs which are taken up by macrophages are incorporated into TGs (and cholesteryl esters)
The transforming growth factor-β (TGFβ) ligands are synthesized as a large latent TGFβ complex consisting of mature dimeric TGFβ associated with its latency-associated peptide (LAP) and a latent TGFβ-binding protein (LTBP) (not shown)
In the non-canonical pathways, the activated transforming growth factor-β (TGFβ) receptor complex transmits a signal through other factors, such as TNF receptor associated factor 4 (TRAF4) or TRAF6, TGFβ-activated kinase 1 (TAK1), p38 mitogen-activated protein kinase (p38 MAPK), RHO, phosphoinositide 3-kinase (PI3K)-AKT, extracellular signal-regulated kinase (ERK), JUN N-terminal kinase (JNK) or nuclear factor-KB (NF-kB)
Transforming growth factor-β (TGFβ) has biphasic actions during tumorig enesis, suppressing tumorigenesis at early stages but promoting tumour progression later on, which is the underlying paradigm for the action of TGFβ during disease progression in general and thus complicates the development of therapies targeting TGFβ signalling
Transforming growth factor-p (TGFβ) signalling can be inhibited by: sequestering ligands using soluble receptor ectodomain constructs (ligand traps) derived from TGFβ receptortype II (TpRII) or TpRIII; using TGFβ-neutralizing antibodies; or with TpRII or TpRI kinase inhibitors
The Metabolic Pathway for the Formation of CHB (1) and CBO (2) from BD, and the Subsequent Reactions of CBO with GSH to Form Three CBO-GSH Conjugates (3, 4, and 5)
A. number of stimuli, including growth factors, cytokines, PAMPs, ROS, and environmental stresses activate the JNK signaling pathway through a 3-tier kinase cascade that includes MAP3Ks (ASK1, TAK1, MEKKs and MLKs), MAP2Ks (MKK4 and MKK7), and JNKs.
(A) Schematic structures of NAD(H) and NADP(H).... (B) Oxidized and reduced forms of nicotinamide... (C) Overview of the biological roles of PNs as...
(A)In wild type (WT) animals, BC1 RNA maintains an appropriate neuronal excitability tone at the synapse by inhibiting (red line) protein synthesis stimulated by the group I mGluR– MEK/ERK pathway (green arrows)
Taken from: Alberini CM Chen DY (2012)A number of intracellular signal transduction pathways are activated upon learning by diverse stimuli, such as stress, neurotransmitters, growth factors and membrane depolarization, and lead to activation of the CREB-C/EBP pathway
Illustration of GnRH signaling pathways necessary for FSHβ induction
The membrane receptor TLR3 recognizes and binds internalized extracellular dsRNA only in acidified endosomes, and then activated TLR3 induces type I interferon production via interferon regulatory factor 3 (IRF3) and proinflammatory cytokine generation via the NFŒ∫B pathway
MAPK signaling pathway and B-Raf derangements in gliomas
(A) The lead compound Bu4ManNAc is used for illustrative purposes; if extracellular esterase/lipase degradation is relatively slow (left) then the intact molecule will enter the cell; alternately if ester hydrolysis is relatively fast (right) a partially degraded metabolite such as 3,4,6-O-Bu3ManNAc will enter the cell (B)
Proposed pathway of urinary carnitine loss by cisplatin in wildtype mice (A) but not in Oct1/2(−/−) mice (B)
In bone marrow derived MŒ¶s, IFNŒ± receptor is necessary for optimal expression and IFNŒ±-mediated induction of mA3 mRNA
Impact of IL-27 on lymphocyte signaling pathways
(A) Receptors for IL4 and IL13 are comprised of... (B) In the presence of al signaling receptors,... (C) In the absence of IL13RŒ±2, IL13 may have e...
Upon activation of the phosphatidylinositol 3-kinase (PI3K) pathway downstream of receptor tyrosine kinase (RTK) signaling, AKT is thought to be the major kinase that inactivates GSK3 via phosphorylation of the N-terminal serine residue (S21 in GSK3α and S9 in GSK3β) (1)
Vorinostat reduces the expressions level of HDAC1&2
Ingenuity pathway analysis reveals the close relationship between 14 of 17 of most relevant genes in rectal cancer
Targeting 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) for colorectal cancer prevention and treatment
The GSK-3 serine/threonine kinase promotes MLL-FP-mediated leukemogenesis by increasing the recruitment of HOXA9 and its cofactor MEIS1 to target genes
In responds to specific ligands for TLR3, TLR4, or DDX1-DDX21-DX36 (DExD/H-box helicase) complexes, an adaptor protein TRIF activates the transcription factors, IRF3, NF-Œ∫B and AP-1 to induce various genes
L. pneumophila translocates a large number of effectors into host cytosol via the Dot/Icm type IV secretion system to facilitate its intracellular replication.
Proposed signaling pathways of H2S in cardioprotection: representation of the putative cascade of reactions triggered by molecular H2S
Antigen encounter triggers clonal expansion of naïve CD4 T cells that is mainly dependent on p110δ
Inflammation induces binding of cytokines and inflammatory ligands to their receptors, which in turn activate the corresponding transcription factor signaling pathways
Key proteins involved in the intrinsic and extrinsic apoptotic pathways are depicted focusing on the components with known links to autophagy mentioned in the text
The immunoregulatory role of anchored cAMP signaling in T cells
Binding of TNFŒ± (or IL-1β) to their respective receptors triggers canonical NF-Œ∫B signaling
Peripheral blood monocytes (Mo) were cultured with control medium or with conditioned medium from HCT116 or Hke-3 colon cells for 48 hours
Several mendelian autoinflammatory diseases are caused by mutations in genes encoding proteins that directly or indirectly regulate interleukin -1β (IL-1β), an important mediator of fever and inflammation
Members of WNT signaling pathway predicted by MIRANDA algorithm to be targeted by miRNAs that are significantly differential expressed early in the NM-A-AC sequence (yellow) or that are significantly correlated with nuclear expression of β-catenin (orange)
Stochastic signaling pathways regulated by oncogenic Ras in the induction of apoptosis
Schematic illustration of mechanisms causing impaired insulin signaling in vascular endothelial and smooth muscle cells
FPR1 on GBM is activated by tumor and host cell-derived agonists, including Anx A1 released by necrotic tumor cells
Molecular signaling alterations induced by intracellular delivery of CagA
Integrated scheme for MIF expression, signal transduction and regulation of glucocorticoid immunosuppression and cell survival
Schematic diagram showing the intracellular signaling pathway by which angiotensin type-2 receptors (AT2Rs) and dopamine -1 receptors (D1Rs) interact in the control of Na+ transport
Components for which mutations have been identified in telomere syndromes are indicated in bold type and shaded in blue
VEGFA and BMP pathways have distinct as well as overlapping intracellular targets
Networks of low-dose radiation responsive genes linked to carcinogenesis
Model of Ras activation by ‚Ä¢NO-mediated processes in pancreatic cancer
Retinoic acid signaling pathway for neurogranin expression
Innate immune stimulation by LPS positively impacts T cell priming
After infecting a host cell, RNA viruses replicate their RNA, which contains 5‚Ä≤-triphosphate and double-stranded segments that are recognized by the cytosolic sensor protein RIG-I
Upon engagement of MHC-bound peptides, T cell receptors (TCR) trigger a cascade of tyrosine phosphorylation events that lead to the activation of protein kinase C-Œ∏ (PKCŒ∏)
A. During glial-guided of migration of CNS neurons in the developing mammalian brain neurons are polarized in the direction of migration (arrow).
Generalized schematic representation of the BMP signaling pathway
(a) The glucosinolate (GLS) pathway. GSH, glutathione. (b) Glucosinolate hydrolysis to form epithionitrile, nitrile, thiocyanat...
PGN-induced miR-132 and miR-212 in TLR signaling
The pathways inside the circle shows the most important pathophysiological pathways in the generation of aGVHD
Model based on Panther Pathway diagram (http://www.pantherdb.org).
After TNF stimulation through TNFR, GAPDH is induced to the TRAF2 complex, promoting TRAF2 polyubiquitination and activating the NF-Œ∫B pathway through IKK
Chemical factors influence the cellular response to mechanical factors and vice versa
Schematic of the effect of chronic oxidative stress on the insulin signaling pathway
PIAs recapitulate the activity of two tumor suppressors that converge on mTOR
PIKE GTPases protect the neuron from excitotoxicity-induced dysfunction and cell death by dual mechanisms: they limit the ampount of Ca2+-impermeable AMPA-R (GluA2) on the cell surface to prevent excessive Ca2+ influx and activate the PI3K/Akt pathway to block the death signaling induced by prolonged elevation of intracellular Ca2+ concentration ([Ca2+]i)
Interstrand crosslink (ICL) recognition by FANCM and associated proteins leads to the recruitment of the Fanconi anaemia (FA) core complex and monoubiquitylation (Ub) of FANCD2–FANCI
In cells in G1 phase of the cell cycle, nucleotide excision repair (NER) can remove a subset of interstrand crosslinks (ICLs)
Model for signaling pathways involved in v-src induced initial closure of Cx43: The hypothetical model shown is based on the data presented here, and established (solid lines) or proposed connections (dashed lines) from other studies (see text)
Connecting the Insulin pathway to the Drosophila autophagy machinery
Proposed scheme, illustrating the involvement of TRPV4 in mechanosensitivity in the distal nephron cells
Cytoscape diagram of the functional interaction network representing proteins modulation in Pt1 interstitial fluid
The phosphatidylinositol (PtdIns) phosphates, PtdIns(4,5)P2 and PtdIns(3,4,5)P3, are key signaling molecules in lymphocyte activation
Biochemical relationships between the CDP-choline pathway of PtdCho synthesis, the degradation of PtdCho, and general phospholipid metabolism in mammals
A. Pathways for the major phospholipid components are shown including the de novo pathway for phosphatidylcholine (PC) synthesis.
Oncogenic pathways in ABC-DLBCLThe stimulation of several surface receptors, including the B-cell receptor (BCR), CD40 or Toll-like receptors, triggers signaling cascades resulting in the activation of the NF-kB pathway
Engagement of CD47 by TSP1 inhibits its lateral interaction with VEGFR2 and modulates signaling mediated by Ca2+, cGMP, and cAMP in vascular cells
PYO produced by Pseudomonas aeruginosa enters the cytosol of airway epithelial cells and produces reactive oxygen species (ROS) by oxidizing its intracellular NADPH pool
The structure of PA is shown with fatty acyl groups of 16:0 (sn-1) and 18:1 (sn-2)
Proposed mechanism for opioid modulation for TLR
Shown are the major signaling pathways involved in the regulation of spine remodeling and synaptic plasticity, including NMDA and AMPA glutamate receptor subtypes, neurotrophic factors (i.e., BDNF), and related downstream signaling, particularly the ERK and Akt pathways.
Schematic presentation of the proposed involvement of signaling pathways in expression of P450s and extracellular lignin degrading enzyme system (LDS) in P
Role of mesothelin in cancer progressionOverexpression of mesothelin leads to higher IL-6 production by constitutively activating NF-Œ∫B
Shown are mechanisms that involve the RANKL-stimulated Ca2+ signal pathway
The oxidative pentose phosphate pathway (PPP; red arrows) generates NADPH to maintain reduced glutathione, combat reactive oxygen species (ROS), and maintain redox homeostasis
Pathway analysis of genes highly expressed in TNBC compared to HR-positive, HER2-negative breast cancer
Schematic diagram shows how Ca cycling proteins and other regulatory parameters affect Ca alternans via the common pathway of the 3R’s
SIRT1 in the brain is involved in a number of processes that affect neuronal health, neurogenesis, and behavior
Six important signaling networks of osteoblast differentiation
shows the effects of osteoblast-secreted osteocalcin on glucose homeostasis and its novel role in regulating testosterone production in the leydig cells
Hypoxia stimulates AKT and mTOR activation hence repressing inhibitory effects of class I PI3K inhibitor GDC-0941
Arachidonic acid, a constituent of cell membrane lipid domains is released by phospholipases, especially a cytosolic phospholipase (PL)A2, mobilized by physical and chemical stimuli, and is subject to metabolism by prostaglandin (PG) G/H synthases to form sequentially PG endoperoxides, PGG2 and PGH2
The diagram of the signaling cascades in TLR pathway
Crosslinking of FcεRI-bound IgE with antigen induces aggregation of two or more FcεRI molecules and activates the protein tyrosine kinases LYN and FYN
The conserved role of IGF-I in lifespan regulation and stress resistance
An early event in the cellular response to gallium(III) is an increase in intracellular ROS of mitochondrial origin
The WNT pathway in a normal, adult, colonic epithelial cell is depicted on the left-hand side of the Figure
O6MeG lesions are converted to O6MeG/T mispairs in the first replication cycle
(A) Mutation significance analysis, using the MutSig2.0 and GISTIC2.0 al... (B) The significantly mutated genes fall into seven core signaling pathw...
Photic input from the RHT drives the release of the excitatory amino acid glutamate and the neuropeptide PACAP
At the excitatory synapse, the cell adhesion molecules neurexin and neuroligin and structural proteins in the postsynaptic density, including Shank proteins, regulate, and are regulated by, neuronal activity-dependent signalling networks
Activation of NMDA receptors and L-type voltage-sensitive calcium channels (L-VSCC) trigger calcium influx and induction of calcium-dependent signalling molecules, including CaMKK that activates the kinases CaMKII and CaMKIV, calcium-sensitive adenylyl cyclases (AC) that activate PKA, and the calcium dependent phosphatase calcineurin
A TCR complex on the surface of T cells recognizes a specific antigen-MHC complex on an antigen-presenting cell (APC)
Genetically associated genes (dark blue) interact to form a common network although some of the interlinking genes (sky blue) to complete a biological pathway
IBD/CHD associated genes are connected through small molecules and share a common biological pathway
Various small molecules interact with shared ADs genes suggesting that SNPs in these genes could be modulated through these factors
A. Relative levels of some of the prostanoids produced by classically activated mouse bone marrow-derived macrophages differentiated in the presence of a normal (5.5 mM) glucose concentration and then stimulated with LPS and IFNγ for 48 h. B.
When naive 5C.C7 CD4+ T cells receive strong TCR signals, strong and prolonged ERK activation is induced.
In mammals, there are four Notch receptors, Notch 1–4, and five Notch ligands, Jagged (Jag) 1 and 2, and Delta-like (Dll) 1, 3, and 4
Relationships between members of the protein kinase superfamily (kinome dendrogram reprinted with permission from Cell Signaling Technology, Inc. and Manning et al. ))
AD. Illustration of pathophysiological pathway in chronic and acute AD.
PGC-1Œ± is activated via post-transcriptional phosphorylation by AMPK or by deacetylation via SIRT1 in response to nutrient deprivation
Summary of radiation-induced long-term alterations, local and systemic, in relation to mammary glands
A working model for the role of TAK1 lysine-72 in the negative regulation of TNFŒ±-induced NF-Œ∫B activation
The mammalian target of rapamycin (mTOR) associates with distinct sets of adaptor proteins to form the mTORC1 and mTORC2 signaling complexes
Arachidonic acid is metabolized through three enzymatic pathways
Communication between the prostate mesenchymal (orange) and epithelial cells (green) is essential for normal prostate development
Prostate development progresses from the undifferentiated UGS epithelium and stromal cells to the invasion of the mesenchyme by the developing epithelium
CBF and CFTR are activated through the PKA-dependent pathway
Pattern-recognition receptors (PRRs) and signaling pathways that lead to differentiation of antifungal T helper (Th) cells
Schematic summarizing the effects of MIF on the canonical MAPK pathways
Lipid (fatty acid) metabolic pathway diagram from KEGG Pathway analysis
(A) TGFβ post-transcriptionally regulates MMP9 through SMAD2/3 and MLCK... (B) EGF activates Erk1/2 and AKT pathways to promote EMT. EGF activates...
(A) LEM2 is a negative regulator of ERK signaling during muscle differen... (B) During myogenesis, NET39 acts as a repressor of the mTOR-IGF-II sign...
mTORC1 modulates cell response (cell growth and proliferation) to nutrients and is a key suppressor of autophagy
Simplified schematic of signaling pathways driving resistance to BRAF inhibitors
A model for regulation of LTP induction in the hippocampus by NRG1-ErbB4 signaling through suppressing Src enhancement of NMDARs
Pathways regulating intestinal sterol absorption and homeostasis
The figure illustrates the steps that lead to the activation of ATR
Pro-osteoblastogenic signal transduction by insulin and IGF1 receptors
Potential cross-talk between insulin/IGF-1, BMP2, and Wnt signaling pathways
PAFAH1B1 (platelet-activating factor acetylhydrolase 1 regulatory subnuit 1, formerly known as LIS1)-binding partners
CDK5 phosphorylation substrates during neuronal migration
Insulin receptors in endothelial cells co-localize with cavaolae, and insulin signaling in endothelial cells leads to two downstream signaling pathways
PI 3-kinase branch of insulin signaling regulates NO production and vasodilation in vascular endothelium
Endothelial dysfunction and endothelial insulin resistance co-exist in the state of insulin resistance including metabolic syndrome, obesity and diabetes
Schematic representation of signaling pathway by which β-catenin may regulate intricate inflammatory responses in liver IRI
The TLR3 signaling pathway is mediated exclusively by the TRIF adapter
Stimulation of cells with IL-1β leads to the activation of the ubiquitin E3 ligase TRAF6, which catalyzes the synthesis of unanchored K63 polyubiquitin chains that bind to the TAB2 subunit of the TAK1 kinase complex, resulting in TAK1 activation
After infection by RNA viruses, viral RNA binds to RIG-I and induces a conformational change that exposes the N-terminus of RIG-I which binds to unanchored K63 polyubiquitin chains synthesized by TRIM25 and Riplet
Signaling mechanisms of the five major endothelium-derived hyperpolarizing factors (EDHFs)
5–HT neurons coexpress a gene battery encoding 5–HT synthetic (Tph2, Aadc, Gch1, Gfrp, Ptps, Qdpr), reuptake (Sert), vesicular transport (Vmat2), autoreceptor signaling (Htr1a, Htr1b) and metabolism (Maoa, Maob) proteins
RIG-I and MDA5 helicases are both represented in open conformation upon recognition of intracellular viral RNA, and MDA5 is shown to be interacting with the adaptor molecule MAVS at the mitochondrial outer membrane
There are 4 estrogen and estrogen receptor signaling pathways
Estrogen can reduce Aβ production by favoring the non-amyloidogenic pathway of APP processing through activation of the MAPK/ERK or PKC pathways, while simultaneously promoting Aβ clearance in several ways, such as stimulating microglial phagocytosis and degradation as well as regulating levels of major enzymes involved in Aβ degradation
Farnesoid X receptor (FXR) mediates effects on multiple metabolic pathways in a tissue-specific manner
Possible pathways leading to inhibition of extracellular signal regulated kinase (ERK)1/2 phosphorylation by A2B adenosine receptors (A2BARs)
Kaempferol’s Effects on the MAPK Pathway
Cells were treated with METi or control and phosphorylation/activation mapping by Reverse Phase Protein Microarray (RPMA) was obtained on three cell lines that comprised the top quartile of the highest HGF expression (U1242, U87, A172) and on four cell lines that comprised the bottom quartile of HGF expression (ONS-76, DAOY, GFM-10 and T98G)
Model of insulin/IGF-1 signaling pathway in vector arthropods
Model of TGF-β1 signaling pathway in vector arthropods
T cell signaling pathways and protein phosphorylation sites identified to be differential between NOD and B6g7 mice in stimulated cells
TMZ triggers loss of K+i, Cl−i and apoptotic volume decrease (AVD), and leads to apoptotic cell death in glioblastoma cancer cells
Pictured are various proposed transporters and their predicted transport mechanisms: SLC41A1/A2 (channel transport mechanism based on structural homology with prokaryotic MgtE transporters); Mrs2, a mitochondrial Mg2+ uptake system that transports Mg2+ with ŒîŒ® (channel transport mechanism based on similarity with yeast Alr family); TRPM7 channel kinase (channel transport mechanism), and MagT1 (thought to be a plasma membrane Mg2+ transporter with an ion channel transport mechanism)
PI3K/Akt/mTOR signaling in breast cancer
Cellular injury associated with hypoxia and inflammation promote the release of ATP that is subsequently dephosphorylated by membrane bound CD39 and CD73
simplified and unified view of the multi-level cross-talk
The EGFR signaling pathway exerts its biological effects via two major modes of actions, namely, the cytoplasmic/ traditional (a) and the nuclear (b) signaling modes.a.
Recognition of nucleic acids by innate immune cells triggers cytokine production
Cancer cells undergo metabolic re-programming
Neutrophil pathway (left side): TMPD treatment results in the release of IL-1Œ±, likely from necrotic cells
(A) Pathways implicated in respons... (B) Epidermal wounding by microinj... (C) Infection by the bacterium M.... (D) Osmotic stress may be sensed b...
(A) Sox2 activates self-renewal genes and represses differentiation gene... (B) In addition to activating self-renewal genes and suppressing lineage...
Subnetworks identified from TCGA ovarian cancer gene expression data set
Enriched pathways and GO functional annotations are
Proposed synergistic pathway to mitotic cell death in cells treated with a combination of paclitaxel and gefitinib or the PLK1 inhibitor BI2536
(A) Tip cell dynamics are regulated by Sema3E-Plexin-D1 modulating Dll4-Notch signaling via a VEGF-induced negative feedback mechanism []
(A) Self-renewal mechanisms in mouse ESCs
LH signaling through its receptor activates cAMP/PKA followed by the ERK pathway, leading to increased levels of LRBP
Regulation of Akt Activation by the PI 3-K pathway
IGF-1R and EGFR/HER2crosstalk occurs by two main mechanisms
The extracellular Ca2+ homeostasis is maintained by the coordinated actions of hormones, bone cells and balanced uptake and excretion of Ca2+ in intestine and kidney
Three important pathways converge on PI3K signaling, including the B cell receptor (BCR), thought to be the dominant pathway in CLL, as well as receptor tyrosine kinases (RTKs) and cytokine/chemokine receptors
Replication forks may inevitably encounter DNA adducts that are not repaired (such as a 6‚Äì4 photoproduct)
High fidelity DNA polymerases stall upon encounter of an interstrand crosslink (ICL) in DNA
Signalling regulation of mammalian autophagy
a | In the nuclei of non-proliferating cells, RB remains hypophosphorylated and forms RB–E2F repressor complexes to inhibit the expression of genes that promote S phase entry
Model of the multi-step pathway of CENP-A-containing centromeric chromatin replication utilizing sequential, temporally separated steps across the mammalian cell cycle
The role of mTOR in CD4+ T cell differentiation
Model of TGF-β restoration by SMAD6 knockdown
LRH-1 binds and activates the promoter of cyclin E1
A simplified version of the insulin signaling pathway
Schematic overview of the E2-mediated modulation of Gαi,o-coupled (μ-opioid and GABAB) receptors via a membrane-associated receptor (mER) in hypothalamic POMC neurons
In a series of enzymatic steps, Vitamin A (retinol) is metabolized through the oxidizing action of retinaldehyde (RDH) to retinal, and by retinaldehyde dehydrogenase (RALDH) to retinoic acid (RA)
Under conditions where RARŒ± is functional and the RARβ promoter is not epigenetically silenced, physiological levels of RA can activate RARβ expression
Schematic presentation of the pathway for interleukin-1β (IL-1β) induced human corneal endothelial cell (CEC) migration that is mediated by fibroblast growth factor-2 (FGF2) expression dependent on parallel activator protein-1 (AP-1) and nuclear factor -Œ∫B (NF-Œ∫B) activation
Blue symbols indicate a gene is under- and red symbols indicate a gene is over-expressed in the pre- compared to the post-surgery samples, grey symbols indicate a gene is not differentially expressed, orange circles indicate that a gene is targeted by one or more of the five miRNAs, each represented by a black symbol on the circle
Pathway analysis of significantly changing expression sub-networks in LMB hypothalamus
A proposed model for PDGF-D signaling pathway that controls the processes of EMT
Modeling spatially restricted biochemical reactions
Feed-forward relay for decoding signal duration
ROS-dependent signaling pathway activated by s-flow, which induces eNOS-mediated NO production and subsequently increases mitochondria-derived H2O2
Ischemia-reperfusion injury in the diabetic myocardium is multi-factorial and complex
This figure shows the modules that could be used to describe interactions between the growth factor and β-adrenergic receptor pathways
Networking and activation of a positive feedback loop by norepi-nephrine acting through the α1- and α2- adrenergic receptor pathways.When norepinephrine (NE) binds the α1 adrenergic receptor it activates the Gq pathway, leading to stimulation of the phospholipase C-β
Multiple strategies have been employed to pharmacologically target the VEGF signaling pathway
(A) The Myc transcription factor represses the... (B) NF-Œ∫B is a transcriptional activator of mi... (C) Myb transcriptionally activates miR-15a, wh...
Summary of several known kinases (blue/purple diamonds) and RNA binding factors (orange/red ovals) that have been shown to be regulated in response to antigen (Ag) stimulation or Fas Ligand (FasL) signaling in T cells, and the genes (text) that they regulate
Pharmacological strategies to overcome resistance to apoptosis in cancer cells treated with PI3K/mTOR inhibitors
A. The MUC1-C subunit forms complexes with EGFR at the cell membrane that are mediated extracellularly by galectin-3 bridges ().
The MUC1-C cytoplasmic domain contains a SAGNGGSSLS motif that binds directly to the β-catenin Armadillo repeats (insert) (; )
A. Schema for a MUC1-C/STAT1/3 auto-inductive loop involving activation of MUC1 and other STAT1/3-dependent genes.
The Wnt3a/β-catenin pathway directly activates Msgn1 and Dll1
Simplified scheme of the complement activation network
Model for the control of ERŒ± expression and cardioprotection by MEF2 and class II HDACs
Several distinct pathways sense dietary input from nutrients in the environment
(A) A variety of environmental triggers modulat... (B) Additional environmental factors stimulate... (C) In addition, genotoxic stress by hydrogen p...
Diversity in endothelium- dependent dilator pathways in the human microcirculation
Overview on the mechanisms of glutathione induced cell death
Regulation of angiogenesis by microRNAs (miRNAs)
Genes and signaling pathways involved in ureteric budding
Genes and signaling pathways involved in ureter development
The role of NAMPT in mammalian NAD metabolism
Ingenuity Pathway Analysis (IPA) was performed with proteins where SUMO3 conjugation was 2- or more fold up-regulated in any gel slice
Central roles for BDNF in the beneficial effects of exercise, dietary energy restriction and cognitive challenges on brain health
GŒ±s (, this study), PKA-C1 (this study) and adenylate cyclase AC3 (at least in PDF-positive sLNvs) () are positive components of PDFR signaling
VEGF triggers autophosphorylation of VEGFR2 (Y1175), which is internalized inside endocytotic vesicles and leads to PLCγ1 phosphorylation in TXNIP-dependent
Leptin and adiponectin activate signaling components that integrate PI3K/Akt, RAS/MAPK, and pAMPK/mTor pathways
In response to DNA damage, the Mi-2/NuRD complex, like other ATP-dependent chromatin remodeling complexes (such as INO80, SWI/SNF, RSC, and SWR1), might be recruited to the site of damaged DNA, and exerts its function in DNA repair by multiple different mechanisms
(A), an in vivo exposure to stress blocks LTPGABA through activation of kappa opioid receptors (KORs) with subsequent modulation of the NO signaling pathway at a point downstream of NO production
Schematic overview of estradiol-mediated genomic signaling pathway via ERŒ±/β and rapid nongenomic signaling pathways via GPER, Gq-mER, and membrane subpopulation mERŒ±/β
Oncogenic RAS may have both pro-apoptotic and anti-apoptotic functions depending on the status of RAS effector pathways and the apoptotic machinery
a. The induction of pro-angiogenic growth factors (vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 2 (FGF2)) by RAS in neoplastic cells is shown.
BTB restructuring is mediated in part by serine/threonine kinases belonging to the MAPK pathway, which transduces signals received from external stimuli (e.g., cytokines and environmental toxicants)
GLI1 Isoforms and cancer characteristics
Regulation of GLI1 the isoforms by the canonical and noncanonical pathways
A) A majority of cellular mRNAs are degraded by the deadenylation-depend... B) The endonuclease-mediated decay pathway triggers the degradation of s...
Network 1 (antigen presentation, cell-mediated immune response, and humoral immune response) generated by pathway analysis of the hot list
Network 2 (metabolic disease, renal and urologic disease, and molecular transport) generated by pathway analysis of the hot list
Cytokine signaling cascades that influence tropoelastin transcription
a, schematic of the trafficking pathway for PMEL from its site of synthesis in the endoplasmic reticulum (ER) through the Golgi and trans Golgi network (TGN) and the plasma membrane, ultimately to stage I and II melanosomes
Mammalian target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) are both controlled by growth factors, whereas mTORC1 is also regulated by cellular energy status, oxygen, stress, and amino acids (AAs)
AMP-activated protein kinase (AMPK) acts as a metabolic checkpoint under nutrient starvation conditions, translating signals to mTORC1 through direct phosphorylation of tuberous sclerosis complex 2 (TSC2) and Raptor and inhibiting cell growth
Amino acids (AAs), depicted as pink circles, may be sensed A) extracellularly, B) intracellularly, from within the C) lysosome, or through a combination
Schematic diagram of the Shh signalling pathway1
(A) Expression profile of nicotinic and muscarinic receptors within stru... (B) Intracellular signaling associated with nicotinic receptor alpha 7 (...
More than 80 SNPs within the Erb4/NRG1 receptor/ligand pair have been associated with schizophrenia
A model for FOXM1’s role in thyroid cancer
Schematic diagram of transforming growth factor-β (TGF-β) signaling pathway
Purine nucleotide synthesis and its role in regulation of AMPK
Model of TRAIL-activated proapoptotic and antiapoptotic pathways
Proposed mechanisms that link synaptic activity, cerebral vasculature regulation and astrocytic energy metabolism with astrocytic Ca2+signaling
Eicosanoid biosynthesis and EP receptor signaling pathway
The process of recruiting the normal and leukemic stem cells to the BM microenvironment may depend on endothelium-derived SDF-1α
In the BM microenvironment, a complex network of cells, ECM, and secreted molecules work in concert to regulate the normal and leukemic stem cells
The single endogenous GPCR, Ste2 is not expressed in the modified S. cerevisiae strain.
Uncoupling proteins are likely to be controlled at multiple levels, such as transcription, translocation, ligand activation or inhibition and protein turnover
Depending on the cellular context, SRC-3 can coactivate different nuclear receptors and transcription factors to promote multiple hallmarks of cancer
A variety of tyrosine kinase receptors, including the insulin receptor, activate the PI3K pathway, which leads to the activation of both mTORC1 and mTOCR2 ()
A. In enterocytes, the trafficking pathways of cholesterol are multiple: cholesterol intake from micelles via NPC1L1 (pathway I); cholesterol synthesis via HMG-CoA reductase (pathway II); plasma LDL uptake with LDL receptor (LDL R; pathway III); plasma HDL uptake with SR-BI (pathway IV); Cholesteryl ester (CE) formation via ACAT and efflux via chylomicrons (pathway V); and free cholesterol (FC) efflux via ABCG5/8 (pathway VI).
In melanoma, the mutation of BRAF (V600E) constitutively activates the down‚Äìstream kinase MEK1/2, which phosphorylates ERK2
Participation of glucose in NADPH oxidase-mediated superoxide generation
Induction and maintenance of IDO in dendritic cells
Proposed scheme linking metabolic and signaling pathways to insulin resistance in the heart
Intratumoral hypoxia is found relatively frequently in NSCLC, and hypoxia --inducible factor (HIF) is a well-known regulator of VEGF levels
Upon activation by extracellular ligands, EGF receptor dimerizes and autophosphorylates
(A) KRAS is a proto-oncogene encoding a GTPase whose mutations can resul... (B) The BRAF gene encodes a serine/threonine protein kinase that operate...
Several mechanisms may account for the toxic effects of saturated fatty acids: 1
Reawakening of the epithelial–mesenchymal transition (EMT) program in prostate cancer epithelial cells engages signaling interactions among different growth factor pathways and the AR signaling axis
Intestinal free ferric (Fe3+) iron is reduced to Fe2+ by DCTB and enters the cell through the divalent metal-ion transporter 1 (DMT1) and possibly other carriers
Double strand breaks induced by DNA damage are first resected to produce 3’ DNA tails, which become coated by the ssDNA binding protein RPA
Targeted proteomics analysis of experimental rat glaucoma
The counteracting writer EZH2 and eraser KDM6A/UTX form a pair in regulating an important epigenetic mark, methylation at H3 lysine 27
Simplified overview of the TGR5-signaling pathway leading to downstream signaling via cAMP induction
p53 is degraded under homeostatic conditions by its negative regulator MDM2, which is an E3 ubiquitin ligase
Lapatinib, a dual EGFR/HER2 kinase inhibitor, inhibits cell proliferation and survival by blocking the PI3K/Akt/mTOR (previously demonstrated by Gayle et al []) and MEK/ERK pathways
The network was generated using Ingenuity Pathway Analysis (Ingenuity Systems, www.ingenuity.com)
Mechanism of endorepellin dual receptor antagonism and block of angiogenesis
Wnt ligands bind to a receptor complex that includes a member of the Frizzled family and either Lrp5 or Lrp6 (right)
The lin-4 homolog miR-125a/b represses both Lin28a and Lin28b during stem cell differentiation
Insulin signalling attenuates cAMP-mediated lipolysis at multiple steps in adipocytes
Insulin signalling exerts rapid stimulation of glucose transport as well as fatty acid uptake, synthesis and esterification to triacylglycerol (TG)
The activation pathway of pDCs responding to viral nucleic acids and negative regulation of the pDC function by surface receptors
Norepinephrine is released from sympathetic nerves to bind to the α1D-adrenergic receptors (α1D-ARs) that activates protein kinase C (PKC)ε and endothelial nitric oxide synthase (eNOS) to stimulate lacrimal gland protein secretion
The muscarinic, cholinergic Ca2+/protein kinase C-dependent signaling pathway is illustrated here as an example of the EGF and Œ±1D-adrenergic signaling pathways
Acetycholine (Ach) is released from parasympathic nerves and binds to M3 muscarinic receptor (M3AChR)
VIP released from parasympathetic nerves binds to its receptors (VIPACR1 and II) and activates adenylyl cyclase (AC) to produce increase cellular levels of cAMP
In the extrafollicular T cell-dependent (TD) pathway, marginal zone (MZ) dendritic cells (DCs) expressing DC inhibitory receptor 2 (DCIR2) capture protein antigens and present them to naive CD4+ T cells, which subsequently differentiate into T helper 2 (TH2) cells expressing CD40 ligand (CD40L) and interleukin-4 (IL-4)
. Graphic of insulin/IGF1 signaling pathway showing proteins encoded by scanned genes.
Cellular receptors trigger the autophagy following the classic 4 stages, as described in the text
Since excess hepcidin leads to ACD, blocking the signaling pathways responsible for hepcidin synthesis, neutralizing hepcidin's effect on ferroportin or promoting ferroportin function may ameliorate ACD (red lines).Hepcidin production can be effectively inhibited by the following BMP6-HJV-SMAD inhibitors: soluble HJV.Fc protein (Ferrumax Pharmaceuticals), monoclonal anti-BMP6 antibodies, or the glycosaminoglycan heparin sequester BMP6, preventing its interaction with BMPR and membrane anchored HJV; the dorsomophin derivative LDN-193189 inhibits BMP type I receptor activity.
Activation of the nuclear factor-Œ∫B (NF-Œ∫B) pathway downstream of multiple inflammatory cell surface receptors, such as interleukin-1 receptor (IL-1R), Toll-like receptor (TLR), tumour necrosis factor receptor (TNFR) and CD40, triggers the recruitment and ubiquitylation of many molecules with scaffolding and catalytic activities
Plexin-B1 and Plexin-A1 are shown in black, with the intracellular C1 and C2 domains represented by black rectangles and the linker region in between as a black circle
A: ephrin-A-EphA signaling in the... B: ephrin–A-EphA signaling in the... C: ephrin–B-EphB signaling in the... D: ephrin-B–EphB signaling in the...
A: VEGF signaling in the vascular system: The PI3K-Akt pathway is shown... B: VEGF-VEGFR2 signaling in the nervous system: Many of the same protein...
Upon β-AR stimulation, the GsŒ± subunit-bound AC produces cAMP which activates target molecules, PKA and Epac
Disruption of AC5 activates the MEK/ERK signaling pathway []
Signaling pathways involving PKR-mediated inflammation and immune regulation
Estrogen (E)-bound ER, acting as a transcription factor in the nucleus (nuclear/genomic activity), binds to DNA sequences in promoter regions of target genes either directly (at estrogen receptor elements; EREs) or indirectly via protein-protein interaction with other transcription factors at their cognate DNA responsive sites (e.g., members of the AP-1 or the SP-1 transcription complexes at AP-1 or SP-1 sites).
Hippocampal BDNF/TrkB signaling pathways that modulate depressive behavior and antidepressant responses
Ciliary signaling pathways implicated in control of cell proliferation
Inherited predisposition to nerve sheath neoplasia involves germline mutations in key tumor suppressor genes
In the first phase of liver IRI, the ischemia insult induces necrotic cell death, which in turn provide diverse “danger” molecules, such as HMGB1 and DNA fragments to activate innate TLR4, RAGE and TLR9 signaling on KCs/DCs and neutrophils
Signaling network of HER-2-mediated NF-Œ∫B activation in radio- andlor chemo-resistant breast cancer cells
Ligands of the Jagged (JAG1, JAG2) and Delta-like (DLL1, DLL3, DLL4) families (upper cell) interact with Notch family receptors (NOTCH1 through NOTCH4) on an adjacent cell
An arterial endothelial cell is shown on the left, while a venous endothelial cell is depicted on the right
switching the aldosterone response of the kidney to be antinatriuretic (left) or kaliuretic (right)
A schematic representation of glia-mediated detrimental and beneficial inflammatory pathways in PD
Schematic illustration of Wnt1/β-catenin signaling as a key player in neuroprotection via DAergic neuron–astrocyte crosstalk and promoting neurogenesis via neuroprogenitor–astrocyte crosstalk
Schematic illustration of Wnt1/Fzd-1/β-catenin signaling as a candidate regulatory circuit controlling mesencephalic DAergic neuron–astrocyte crosstalk
Regulation of alternative splicing by signaling
In vitro and animal studies have shown that statins exert antineoplastic effects through both HMG-CoA reductase-dependent and HMG-CoA reductase-independent pathways
Model for O-GlcNAcylation in FGF signaling
In response to inflammatory stimuli, dendritic cells produce IL-23 and IL-1β, which induce development of Th17 cells that produce IL-17, IL-22, IL-17F, and other proinflammatory cytokines
Diagram of proposed signaling pathways that modulate phenotypic changes in venous EC in response to VEGF-A
Macrophage stimulation by various TLR agonists results in the release of pro-inflammatory cytokines, whose expression which can be blocked by the Mnk kinase inhibitor
(A) Type I IFN binding to the Type I IFNR leads to the engagement of Erk... (B) Mnk1/eIF4E phosphorylation is induced via IFNγ mediated engagement o...
VEGFR2 and R3 can stimulate MAPK and PI3K signaling pathways in vitro
Common molecular regulators include gene products that affect both autophagy and apoptosis and the pathways that they influence
(A) Signaling pathways triggered by pathogen-as... (B) Mitochondria in mammalian cells are removed... (C) Intracellular bacteria exposed to the cytos...
The inflammatory response, including the recruitment and migration of immune cells to the site of infection and release of cytokines, is mediated by lipopolysaccharide (LPS)
The major signaling pathways leading to cellular apoptosis
The final result of β1-adrenergic receptor stimulation and chronic/intermittent hypoxia is the activation of transcription factors (HIF, CREB, …) and CACNA1H gene expression that lead to Cav3.2 channel incorporation into the plasma membrane.
Methylation and phosphorylation are two major post translation modifications of PP2A
A-B. Interphase Golgi membrane fusion mediated by NSF (A) and p97/p37 (B).
Signal 1 results from MHC–antigen recognition through the T-cell receptor–CD3 complex, a process blocked by anti-CD3 mAbs and indirectly by rituximab
Upper panel: In resting conditions, the stress sensors IRE1 and PERK and ATF6 interact with Bip/GRP78
IL-10 signaling pathway at two hours is differentially expressed between the PT and TH murine models
The genes encoding cell cycle regulatory subunits (e.g.
Mechanisms underlying molecularly targeted therapeutics-induced cardiac toxicity
IQGAP1 binds receptor tyrosine kinases (RTK) like EGFR [] directly or indirectly to signal the formation of specialized scaffolds, which regulate cell homeostasis through dynamic phosphorylation [, , , ]
A model for the observed effects of Hedgehog and Wnt inhibition, and Sox17 overexpression in HOG cells
(a) PA can be generated by three major mechanisms – first by the de novo... (b) PA is generated from the glycolytic intermediate DHAP. Glycolysis re...
The regulatory/signaling pathway modules of identified proteins were analyzed by DAVID and STRING 8.1 (http://www.string.embl.de/).
A. Inhibitory stress kinase regulation of insulin signaling and heat shock protein (HSP) expression.
A figure illustrating a link between the neurobiology of depression and the mechanisms through which ketamine produces its antidepressant effects.A.
MiR-221/222 act as oncomiRs by targeting important tumor suppressor genes such as PTEN, TIMP3, p27Kip1, p57, Bim
ALPS is caused by defective Fas-mediated apoptosis
A) Overview of screen and data analyses. B) Unsupervised hierarchical clustering of mapp... C) Mapping of SLuGs onto the Wnt/Tankyrase/β-ca...
The TCR transmits signals through the LAT-SLP76 complex, and possibly through GLK to activate PKCŒ∏
Independent lines of evidence show that many CNS inhibitors and their receptors are present at or near synapses
The exact mechanism of PAI-1-regulated apoptosis is not clear and several different scenarios are possible
A hypothetical pathway leading to neuronal degenerationDamaged protein accumulation appears due to aging, mutations in genes and environmental factors
Arachidonic acid (AA) is obtained either directly from diet or synthesis from linoleic acid
Hypothetic models for the role of F-CPE and ŒîN-CPE in Wnt signaling
Musashi signaling pathways associated with mammary progenitor cell expansion
A module that correlates with multiple LOAD clinical covariates and is enriched for immune functions and pathways related to microglia activity (PFC module shown)
The ER luminal chaperones gp96 and PRAT4A are responsible for proper folding and function of TLR1, TLR2, TLR4, TLR7 and TLR9, but not TLR3
A schematic showing some major pathways implicated in cancer progression using Drosophila studies
Canonical ATR signaling pathway and functions of newly identified regulators
In the canonical Wnt/β-catenin pathway (shaded grey), the signal is transduced through Dishevelled (Dvl) upon Wnt protein binding to its receptor Frizzled (Fz)
Alterations of the AKT pathway in human cancer
Modules specifically responsive to the influenza (A) or pneumococcal (B) vaccines were subjected to pathway analysis
MK-8776 inhibits Chk1 autophosphorylation (Ser296) that is required for maintaining basal Chk1 activity during DNA replication in S phase
Cues that induce and inhibit protein synthesis antagonistically regulate the activity of mammalian target of rapamycin (mTOR), which regulates cap-dependent mRNA translation by phosphorylating its two major targets: eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (S6K)
Aspirin targets multiple components of the AMPK/mTOR signaling pathway in colorectal cancer
Molecular pathways of memory reconsolidation
A schematic representation of the proposed mechanism by which high glucose, via its effect on peroxynitrite, inactivates the VEGF/PI3K/Akt-1 pro-survival pathway and stimulates cell death via activation of p38 MAP kinase pathway
EGF and TGFŒ± are typical growth factors that transduce growth signals via EGFR (HER1), which is one member of the ErbB family of receptor tyrosine kinases
Under physiological conditions, activation of TGFβR complex I and II following TGFβ binding results in G1 cell cycle arrest (through the inhibitory activity of P21WAF1/CIP1) (central panel)
The signaling pathways activated either directly or due to cross-activation is MAPK and AKT/mTOR signaling
IRE1Œ±- and PERK-mediated cell death pathways
The apoptotic pathways regulated by the UPR
The nine genes with significant mutation frequencies fall into five core signaling pathways, in which the genes play well-established roles: DNA damage repair and cell-cycle control (Panel A), Notch signaling (Panel B), inflammatory pathways (Panel C), Wnt signaling (Panel D), and RNA splicing and processing (Panel E)
Ras1 regulates mating, morphogenesis, and thermotolerance via a branched signaling pathway
Nodes are the proteins and edges are the interactions
CREB phosphorylation may be inhibited through inhibition of the PKA pathway, the Uch-L1 proteasomal system, aberrant calpain activity, or inhibition of the cGK pathway
(a) Model depicting the role of Wls/Gpr177 in regulating the Wnt signali... (b) Involvement of Wls-regulated Wnts in the hair cycle. E, epidermis; D...
Binding of the chemokine (red) to the GPCR involves interaction of the N terminus of the chemokine with the N terminus of the receptor
TGF-β and TNF-Œ± increase ROS production, which, by activating the MAPK pathways and/or the NF-Œ∫B pathway, increase the transcription rate of the PAI-1 gene
Rings of data depict different measurements about genes or proteins as higher activity (red) or lower activity (blue) compared to normal controls
Predicted gene presence calls for the Western diet microbiome and/or the E.dolichum genome are displayed in the upper right.
The different layers of the epidermis, and the functions within those layers regulated by VDR and its coactivators
Schematic model of FGF-2 and FGF-18 signaling pathways in articular cartilage and IVD
The principal cells controlling body iron and copper homeostasis are shown with points of interaction between the two metals indicated by a star (★)
Pathways that control levels of macroautophagy
Schematic of TCR signaling pathway leading to NF-Œ∫B and JNK activation
Schematic of the possible mechanistic roles of platelets in cancer metastasis
Mechanisms by which rotaviruses cause diarrhea
Schematic outline of the regulation of EGFR internalization and mediated signaling by the CIN85–SH3GL2–Cbl complex
A network of upstream signaling pathways comprised of the oncogenes and tumor suppressors listed control the activation status of mTORC1 by regulating the TSC1-TSC2 complex
(A) The figure shows the canonical insulin signaling pathway leading to... (B) Inositol-derivatives serve as signaling molecules when phosphorylate...
Schematic of signal transduction in MMTV-Pax8PPARγ mice
Activation of the calcineurin-NFAT pathway
Regulation of the calcineurin-NFAT pathway
NFATc1 as part of the non-canonical Wnt-Frizzled pathway
Interaction networks of significantly regulated genes from interconnected neurons 7 days post-infarct
Trigger factors such as allergens, bacteria, mechanical injury, and exogenous proteases induce the release of IL-33, IL-25, and thymic stromal lymphopoietin (TSLP) from keratinocytes
Free radical-producing MDRC are master regulators of airway inflammation.The three subsets of the myeloid lineage cells defined here express and use metabolites of the free radical pathways to differentially regulate T cell proliferation, Treg cell chemotaxis and AHR
MAPK signaling transduction in mammalian cells
TLRs signal as dimers and heterodimers that recruit adaptor proteins such as CD14 and MD2
The MRN complex or Ku70/80 heterodimer recognizes and binds directly to broken DNA ends
In a subgroup of cancers harboring wild-type KRAS (left), a specific receptor tyrosine kinase (RTK) (e.g., epidermal growth factor receptor [EGFR]) controls the PI3K–AKT and MEK–ERK signaling pathways, which are down-regulated by RTK inhibition., Cancers with mutant KRAS (right) have constitutive activation of the MEK–ERK pathway (and possibly the PI3K–AKT pathway).
Binding of fibroblast growth factor (FGF) to the FGF receptor (FGFR) induces FGFR dimerization, which juxtaposes the intracellular Tyr kinase domains of the receptors so that kinase activation by transphos- phorylation can occur,
Figure shows a schematic for mechanisms by which calcium entry may induce cell signaling based on the literature and our hypothesis
a) Schematic representation of molecular mechan... b) Schematic representation of classical metabo... c) Schematic representation of alternative meta...
PTHrP is secreted from the mammary epithelium (pink) and acts on the mammary mesenchyme (blue) to activate signaling via β-catenin
Comparison of CK2 knockout defects and Wnt pathway knockout defects, with a schema to indicate where in the pathway CK2 is believed to act
Cells were incubated in medium alone or pretreated with 0.01 mM of doxycycline for 24 h, followed by incubation with fresh 0.01 mM doxycycline and sonicated B. burgdorferi (10 MOI-equivalent) for 2 or 12 h. Pathway analysis was performed using Ingenuity Pathways Analysis (IPA) software, version 5.0.
Signaling pathways activated in cord blood-derived CD34pos hematopoietic progenitor cells (upper panel) and in erythroblasts at day 6 of differentiation (erythroblasts, lower panel)
a | To promote antigen-specific immune responses during priming in the lymphoid organs, distinctive co-stimulatory pathways can be engaged, such as CD28, CD137 (also known as 4-1BB), CD27, OX40 and CD40, by agonistic reagents or through blockade of the primary early checkpoint receptor cytotoxic T lymphocyte antigen 4 (CTLA4) by an antagonist
Summary of events leading to the generation of cytosolic reactive oxygen species (ROS) (R1) and mitochondrial ROS (R2)
As described in the text, factors associating with specific RNAs, often through USER codes, underlie formation of specific export mRNPs
Angiogenesis signaling pathways in epilepsy
Ligation of T-cell PD-1 by B7-H1 on APC leads to the formation of PD-1/TCR microclusters and the subsequent recruitment of SHP2 phosphatases, which dephosphorylate multiple members of the TCR signaling pathway
Model of TLR4 and chemokine receptor crosstalk
Upon engaging a cognate receptor complex (IFNAR1-IFNAR2 for Type 1 IFN, IFNGR1-IFNGR2 for Type 2 IFN or IL28RA-IL10R2 for Type 3 IFN) IFN activate receptor-associated JAKs
Following ischemic injury, ROS production is increased in entire BM in a Nox2-dependent manner, which is required for increasing hypoxic niche and its downstream HIF-1α and VEGF expression throughout the BM
When eosinophils are activated by hyaluronic acid, it triggers ERK phosphorylation by the Ras/Raf/MEK pathway
PI3K/AKT activation in myoblasts C2C12 regulates myomiR maturation via the ARE-BP KSRP
Resveratrol readily activated the AMPK-SIRT1-PGC-1Œ± pathway in this rat model
Models to explain the AD series of compounds in dRetMEN2B transgenic flies
The Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R)-family members share several signalling components, including the adaptor MyD88, Toll-interacting protein (TOLLIP), the protein kinase IRAK (IL-1R-associated kinase) and TRAF6 (TNF receptor-associated factor 6)
a ∣ The expression of interleukin-10 (IL-10) can be induced by Toll-like receptor (TLR) or non-TLR signalling in macrophages and myeloid dendritic cells (DCs)
Proposed model for NV-128-induced casapase-independent cell death in OCSCs
Schematic diagram illustrates OxyHb-induced KV current suppression via enhanced MMP activation and HB-EGF shedding
miR-181b and miR-146a induced in CAFs are involved in the regulation of the NF-kB signaling pathway
Schematic of the enhanced mathematical model used to represent the Gq-mediated calcium signaling pathway
(A) Hh signaling in Drosophila. In the absence of Hh (left), Ptc prevent... (B) Hh signaling in vertebrates. Hh signaling in vertebrates is similar...
These images represent the evolving picture of medicine that is driving the development of nanotechnologies for the investigation, diagnosis, and treatment of cancer
Signaling pathways involved in the regulation of microglial immune activities were highlighted in the analyses of genes whose expression varied significantly as a function of age
(A–B) Two particular signaling pathways involved in angiogenesis were those involving (A) thrombospondin... (B) vascular endot... (C) Neurotrophic-T...
Activation of the PGC1Œ±-mediated endurance pathway contributes to the enhanced mitochondrial biogenesis and Type I fiber switch seen during hibernation
(A and B) Differences in network architecture shape dynamical responses
Model of MIF Signal Transduction Involving MIF Binding to CD74 and Activation of the CD44 CoreceptorThe pathway leading from the CD44 intracytoplasmic domain through c-Src and toward the activation of guanine nucleotide exchange factors (GEFs) has been described (; )
Vascular endothelial growth factor (VEGF) binds to a homodimerized VEGF receptor (VEGFR), which becomes phosphorylated and activated
Schematic representation of proposed intracellular effects of S100A1, S100A4, and S100A8/S100A9
Schematic representation of S100A8 induction in macrophages
Molecular basis of stomach epithelial specification in embryos
Summary of events leading to the generation of cytosolic ROS (R1) and mitochondrial ROS (R2)
Model for Nitr9L–Dap12 activation of cytotoxic cells
Schematic representation of the proposed signaling pathways for 8-iso-PGF2Œ±-mediated modulation of human platelet function
The ERK pathway, its upstream activators and downstream targets
Diagram illustrating the signaling mechanism of how CARD9 may be inhibiting apoptosis from TNF-alpha
Upon binding Shh, Ptc1 releases the inhibition of Smo
Summary of the effects of increased dietary fat plus ethanol on the AMPK pathway and expression of enzymes involved in fatty acid synthesis
Because thrombin cleaves PAR1 at Arg41 and APC cleaves PAR1 at Arg46, the tethered-ligand sequences generated by these proteases differ and accordingly result in activation of different signalling pathways, which has been labelled “biased agonism.” The agonist bias is thus directly related to the cleavage sites of the tethered-ligand and the new N-terminal sequence as represented by the TRAP peptide that exists after cleavage at Arg41 or the TR47 peptide that exists after cleavage at Arg46 [].
When tumor cell is inflicted with ionizing radiation, the double strands of DNA are broken and the DNA damage response (DDR) pathway is further initiated
Proposed model for the integration of primary afferent, mast cell and sympathetic systems in supporting CRPS-related nociception
A scheme illustrating the mechanism by which WNK4 inhibits BK channels
Potential targeting of PI3K/mTORC1 signaling in hamartoma syndromes
In this model, increased DNA damage (for example, owing to telomere attrition, impaired DNA repair and increased reactive oxygen species (ROS) levels) activates p53, and increasing levels of p53 ultimately lead to compromised mitochondrial function through the repression of PPARγ co-activator 1α (PGC1α) and PGC1β (which promote mitochondrial biogenesis)
WT transcriptome data overlaid on selected metabolic pathways
A functional link between the BMP system and GnRH-induced FSH transcription
CYP1A1 knock down by siRNA results in the dual inactivation ERK and AKT (1)
Interactions between nTreg (A) or IL-2 activated inducible Treg (Tr1) with effector T cells (Teff) mediated by the adenosine and PGE2 pathways
Schematic depicting the canonical and noncanonical TGF-β signaling systems coupled to EMT in MECs
Vaccination can induce both T cells dependent and independent immune responses
TRAIL-mediated extrinsic pathway of apoptosis
Therapeutic targeting of caspase activation signaling.Ligand binding to death receptors (extrinsic pathway) results in death initiation signaling complex activation and signaling through initiator caspase 8
Basal HAMP expression depends upon signaling by interaction between BMPs, BMPRs through the downstream SMAD factors
Schematic depicting the canonical and noncanonical TGF-β signaling systems activated during mammary tumorigenesis
(A) The cell surface Cripto/GRP78 complex interaction required for Cript... (B) The N-20 antibody blocks Cripto binding to cell surface GRP78 and in...
Emphasis is placed on ligands and receptors that activate pathways, the main effectors of each pathway, and their target molecules
In the cytoplasm, NF2 is known to disrupt the downstream signaling of Rac1 and Cdc42 at several points
Multipotent mesenchymal precursors in condensed mesenchymes differentiate into Sox9-expressing osteochondroprogenitors, which segregate into chondrocytes that express high levels of Sox9, and preosteoblasts that express high levels of Runx2 and low level of Col1a1 and Akp
Dose-dependent MeHg-induced gene expression alterations within the Wnt-signaling pathway
Signaling axis exploited in the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) mutant mouse model of prostate tumorigenesis
Two pathways are involved referring as TLR4-MyD88 pathway and TLR4-TRIF pathway
Different signal transducer and activator of transcription (STAT) family members can be activated by interferons (IFNs)
Red lines indicate pathways that promote obesity; green lines indicate pathways that protect
Musashi1 (Msi1)-dependent activation of Wnt and Notch pathways as well as of proliferation in the intestinal progenitors
A proposed model illustrating the effects of reduced TH in thyroid cancer development in ThrbPV/PV-PTU mice
Schematic illustration of mutations causing susceptibility to intestinal inflammation
Nutrient deprivation can activate autophagy through mTOR mediated signaling mechanisms
Oxidative and nitrative signals are derived from oxidative reactions with oxygen or nitrogen species, resulting in the generation of both radical and non-radical molecules
. Schematic diagram showing AR inhibition sensitizes human colon cancer cells to TRAIL-induced apoptosis through both, extrinsic and intrinsic pathway.
Molecular mechanisms of cellular insulin resistance in muscle and liver
The two mechanisms of phase II xenobiotic-metabolizing enzyme induction by phase II inducers
Upon recognition of pathogens, TLR signaling (mainly TLR4) induces transcription of IL-18 and IL-1β
Most TLRs except for TLR3 induce NF-Œ∫B activation through the MyD88 pathway
Model of HIV-1 extracellular Vpr action on astrocytic functions
Viral dsRNAs and 5′-triphosphate-bearing, poly-U rich viral RNAs are recognized by the RLRs (RIG-I, MDA5 and LGP2) that are constitutively expressed in the cytoplasm and that initiate MAVS-dependent signaling leading to activation of IRF3/7 and NF-κB, and ultimately, synthesis of type I and III IFNs and inflammatory cytokines/chemokines
Type I and III IFNs bind to distinct, heterodimeric cell surface receptors, but then activate a similar intracellular signaling pathway involving recruitment and activation of the Janus kinases, JAK1 and TYK2, phosphorylation of STAT1 and STAT2, and the formation of the heterotrimeric transcription factor complex, IFN-stimulated gene factor-3 (ISGF3) comprising phosphorylated STAT1 and STAT2 and IRF9
In systems implementing feedback control, the deviation of a measured output from a desired set-point is assessed
Simplified scheme of the pathways of complement activation
The signaling pathway includes two types of membrane Ser/Thr receptor kinases (TβR-I and TβR-II), the receptor Smads2/3, the co-Smad4, the inhibitory Smad7 and nuclear partner proteins (eg, DNA-binding factors)
Hypersensitive Ras and its downstream mediator kinase Erk block transforming growth factor-β (TGFβ) signaling through phosphorylation of the receptor Smads S2/S3 and thereby inhibit the complex formation with Smad4
Cellular stress activates both sensitizer and activator BH3-only proteins
Schematic showing the functional relationship between the mTOR signaling pathway and several genetic diseases, some of them characterized by the development of vascular tumors
Schematic representation of mechanism of action of GW583340 in sensitive (a) and acquired resistance (b) IBC models
MLCK signaling in endothelial hyperpermeability
Top network associated with 15 predicated targets of miRNA-548 is shown
(A) Grey rectangle: mutant BRAF (BRAFV600E) hyper-activates ERK signaling and promotes tumor cell proliferation and survival, but BRAF and MEK drugs inhibit the pathway and block tumor progression
Tyrosine kinase (TYK) targeting growth factor and proliferation pathways
Working model for how ERŒ± may modulate signaling by TLR-activated DCs
A. Cancer-Associated overexpression of Hh ligands or mutations in genes such as Ptch1 or Smo, which lie upstream of cilia, will only result in activation of the Hh pathway by increasing GliA levels if cilia are present.
Angiogenesis pathway of FAK, EZH2 and Dll4/Notch in cancer-associated endothelial cells
The exocyst complex (comprised of Sec3, 5, 6, 8, 10, 15, Exo70, and Exo84) acts at the first stage of the secretory pathway, where it regulates the translocon in the ER, most likely by phosphorylation of Sec61β, for synthesis of basolateral proteins
A) RIG-I is present in the cytoplasm of the cell in an inactive closed c... B) Ubiquitin conjugation is initiated by an E1 activating enzyme in the...
Schematic diagram summarizing the signaling pathways relevant to this study
Gene expression in keratinocytes related to IL-1 signaling
The bioenergetics-EMT-cancer initiating cell axis in the pathogenesis of epithelium-originated carcinomas: a roadmap in the pursuit of targeted chemo-prevention
(a) Ingenuity pathway profiling and mapping of genes/proteins from ATM‚à... (b) Gene networks linking RRM2 with DNA damage repair pathway proteins....
Semaphorin 3A produces a rapid growth cone collapse (left side)
Proposed model of Cr(VI)-induced carcinogenesis
Canonical inflammasomes are cytosolic platforms that activate caspase-1 in response to pathogen- or danger- associated molecular patterns
In mice fed a high-salt diet, the WNK-OSR1/SPAK-NCC phosphorylation cascade is down-regulated through a low plasma aldosterone level (left panel)
A) Diagram indicating the locations of the vertebrate tight junction (TJ... B) A more detailed diagram of the primary components of the AJ and TJ in...
Sufficient glucose and oxygen levels are required for mTORC1 activation, and many sensing mechanisms have been identified
(a) RB1 pathway indicating genes with mutations in this series. Genes in... (b) Hedgehog pathway with known cancer genes mutated in this series indi...
HCMV virion particles bind to the surface of peripheral blood monocytes and engage multiple cellular receptors leading to the simultaneous activation of several signalling pathways
The classical example of NFŒ∫B is the heterodimer of p50 and p65 and the classical activation pathway entails the release from its association with an inhibitory molecule of the IŒ∫B family
Illustration of the hypoxia-inducible factor (HIF) activation pathway, highlighting hydroxylation and acetylation of HIF-1Œ± depending on cellular oxygen tension, that is, normoxia and hypoxia
Dysregulation of JAK/STAT, Ras/Raf, PI3K/Akt/mTOR, and the NF-kB signaling pathway contributes to HNSCC cancer progression upon activation of multiple growth factors and cytokine receptors
SUMO proteins can be covalently conjugated to targets in the presence of SUMO E1 (SAE1/SAE2, heterodimer), SUMO E2 (Ubc9)
The presence of extracellular (or systemic) and intracellular nutrients are sensed by mTORC1 and stimulate its activation
Inhibitory molecules and therapeutic targets within the Rhopathway
The DDR-adapted model in meiotic silencing
A. TGF-β ligands signal through distinct receptors and Smads that are modulated by adaptor proteins and ubiquitinators.
The TG2-containing adhesive/signaling complexes on the cell surface
Model of the mechanism by which the EGF-induced DMR signal is mediated in UPCI-37B SCCHN cells and its application for HTS of EGFR pathway inhibitors
FGF signalling is initiated by ligand-dependent dimerisation of the FGFR, which leads to the cross-phosphorylation (P) of tyrosine residues in the intracellular domain of the receptor tyrosine kinase (not shown)
Activation of the M-CSF receptor c-Fms promotes proliferation and survival of osteoclast precursors
The effects of insulin on glucose uptake and insulin sensitivity presented here are discussed in detail in the text
The major pathways that are mis-regulated in benign nevi, primary melanoma, and metastatic melanoma and their associated proteins are shown as a pathway map modified from the multiple KEGG pathways
Schematic diagram of the Wnt/β-catenin signaling pathway
p19Arf is induced by potentially oncogenic signals stemming from overexpression of oncogenes such as c-Myc, E2F1 and activated Ras (1)
Pim kinase targets and their roles in inflammation and cancer
1) The FANCD2 and FANCI proteins are phosphorylated on multiple amino acid residues in response to a DNA crosslink
TLR1/2, TLR2/6, TLR4, and TLR5 are expressed on plasma membrane and recognize triacyl lipopeptides, diacyl lipopeptides, LPS and flagellin, respectively
Treg activation: CBA (H-2k) mice were injected with CTLA-4-DCs from CBK mice (CBA mice expressing MHC class I, Kb transgene)
Recombination-independent interstrand crosslink repair pathway in vertebrates
Naïve (red nuclei) IgM+ and IgG1+ B cells (generated using nuclear transfer-IgG1-ES mice) each respond weakly to challenge by antigen and produce few plasma cells (green nuclei), resulting in limited amounts of specific antibodies
Delayed cell death signalling pathways mediate the effects of hypoxia-ischaemia in the brain
Activation of the Hippo pathway, which includes the scaffold protein Salvador (SAV) and the kinases mammalian STE20-like protein kinase 1 (MST1), MST2, large tumour suppressor 1 (LATS1) and LATS2, results in the phosphorylation and nuclear exclusion of the transcriptional co-activator Yes-associated protein (YAP) to impede cardiomyocyte proliferation
The circadian clock mechanism involves transcription-translation feedback loops comprised of a set of core clock genes
a) The intestinal epithelium normally provides an effective barrier to macromolecules, bacterial products, and food antigens, but a small percentage can cross the tight junction (dashed arrow)
Normal complement activation cascade and its regulation
Key mutational and therapeutic targets in melanoma
(A) A variety of extracellular stimuli activate NF-Œ∫B signaling via the... (B) Genotoxic agents can induce nuclear DNA damage which initiates a gen...
Signaling pathway and proposed sites of arsenite perturbation
Ang II increases ROS in skeletal muscle via AT1R and NADPH oxidase dependent mechanisms
Simplified schematic of the cAMP/CREB signaling pathway
There are two major pathways of apoptosis, i.e, the death receptor pathway which is mediated by activation of death receptors and the Bcl-2 regulated mitochondrial pathway which is mediated by noxious stimuli that ultimately lead to mitochondrial injury.
Summary of major signal transduction pathways downstream of chemokine receptors
Schematic representation of pathway interactions among HGF/c-Met, PI3K/Akt, and Notch signaling pathways
Upregulation of HER3 and resistance to anti-HER2 therapies
(a) The canonical function of CD4+ T cells is the provision of help for... (b) The best characterized pathway for CD4+ T cell help in the generatio...
Effects of dietary compounds on extrinsic and intrinsic pathways of apoptosis
Map of molecular interactions involving GADD45 proteins and cell signaling pathways generated using Ingenuity Pathway Analysis software (IPA)
Citrate generate in TCA cycle is exported to the cytosol to fuel the mevalonate and fatty acid (FA) synthesis pathways by conversion to acetyl-CoA by ATP citrate lyase (ACLY)
PCa cancer cells show high rates of de novo lipid synthesis and the enzymes belonging to the pathway are regulated by oncogenic signals
A, High-confidence protein-protein interaction network derived from the STRING database
CD8+ T cell memory and effector differentiation are tightly regulated by opposite signals received from inflammatory cytokines and developmental modulators
(A) In the initial stages of the primary response, stimulation of CD8+ T... (B) As clonal expansion increases the frequency of activated antigen-spe...
A schematic representation of the metabolic routes interconnected with fatty acid oxidation (FAO) is shown
Cultured astrocytes and microglia were stimulated with 5 µM imiquimod or 80 nM CpG-ODN 1826 or both
A proposed model of TRP47 effector function in E
A, IL-6/R and IL-17 activate the NF-Œ∫B and MAPK pathway, which then induce IL-6 gene expression
Pathway diagram of the CTLA4 signaling in cytotoxic T lymphocytes from the IPA
PHLPP suppresses the PI3K/Akt signalling pathway
Schematic representation of computational framework of 3D vascularized bone regeneration within a porous biodegradable CaP scaffold
Pathway analysis depicting cytokine and cytokine receptor interactions relative to position in the cellular environment
(A) This diagram summarizes known links between inducers (nutrients and stresses), signaling pathways, transcription factors (TFs), cellular processes vital of CLS, and GO terms enriched in the myriocin-responsive gene set
Scopolamine rapidly increases the number, maturation, and function of spine synapses in pyramidal neurons in the medial PFC
Summary of the published data showing gene regulatory relationships for Mef2c in the Dlx1/2–Arx pathway in GABAergic inter-neurons [, ] (a), the Tbr1 cortical neuron developmental pathway [] (b), Mecp2-associated pathways [] (c), and reported MEF2C interactions with CDKL5 and MECP2 [], as well as interactions with FMR1 during synaptic development [] (d)
Four major signaling pathways in the postsynaptic region of a neuron that combine to form a local signaling network
Aquaporin 2 recycling, including endocytosis and both constitutive and regulated exocytosisConstitutive exocytosis occurs independently of aquaporin 2 (AQP2) phosphorylation and involves recycling of AQP2 through a trans-Golgi or recycling endosome compartment
4EBP1=4E–binding protein 1; AMPK=adenosine monophosphate-activated protein kinase; ASK1=apoptosis signal-regulating kinase 1; ATP=adenosine-5’-triphosphate; BAD=BCL2-associated agonist of cell death; eEF2K= eukaryotic elongation factor-2 kinase; eIF4B=eukaryotic initiation factor 4B; eIF4E=eukaryotic initiation factor 4E; FKBP12=FK506-binding protein, 12 kD; FOXO=forkhead box O1; GDP=guanosine diphosphate; GSK3=glycogen synthase kinase 3; GTP=guanosine-5’-triphosphate; IRS1=insulin receptor substrate 1; mLST8=mTOR-associated protein, LST8 homolog; mTOR=mammalian target of rapamycin; mTORC1=mTOR complex 1; mTORC2=mTOR complex 2; PDCD4=programmed cell death 4; PDK1=phosphoinositide-dependent kinase 1; PI3K=phosphatidylinositol 3-kinase; PIP2=phosphatidylinositol (4,5) biphosphate; PIP3=phosphatidylinositol (3,4,5) triphosphate; PRAS40=proline-rich Akt substrate 40; PTEN=phosphatase and tensin homolog; Rheb=Ras homolog enriched in brain; S6=ribosomal protein S6; S6K=ribosomal protein S6 kinase; SIN1=stress-activated mitogen-activated protein kinase associated protein 1; TSC1=tuberous sclerosis complex 1; TSC2=tuberous sclerosis complex 2
4E–BPs=4E–binding proteins; EIF4E=eukaryotic initiation factor 4E; FOXO=forkhead box O1; GRB2=growth factor receptor-bound protein 2; GTP=guanosine-5’-tri-phosphate; mTOR=mammalian target of rapamycin; mTORC1=mTOR complex 1; PDK1=phosphoinositide-dependent kinase 1; PI3K=phosphatidylinositol 3-kinase; PIP=phosphatidylinositol triphosphate; PTEN=phosphatase and tensin homolog; RAPTOR=regulatory-associated protein of mTOR; Rheb=Ras homolog enriched in brain; TOR=target of rapamycin; TSC1=tuberous sclerosis complex 1; TSC2=tuberous sclerosis complex 2
Binding of CTLA4Ig to CD80/CD86 expressed on an antigen presenting cell can prevent na√Øve T cell activation by preventing CD28 mediated costimulation (left panel)
(A) The abundance of the HIF transcription factor is regulated by the 2-oxoglutarate-dependent EglN dioxygenases, which are sensitive to changes in oxygen and metabolism, and by the PI3K–AKT-mTOR pathway, which is involved in nutrient sensing and frequently mutationally activated in cancer
Major elements of the canonical Wnt signaling pathway
Major elements of the noncanonical PCP Wnt signaling pathway
Major elements of the noncanonical Wnt/Ca2+signaling pathway
Major elements of the Rho signaling pathway
Pathway analyses of the 6 selected miRNAs (miR-122, -127, -182, -183, -206 and -375) were performed using IPA
Genes highlighted in gray demonstrate demethylation in invasive cells
Pattern-recognition receptors (PRRs) recognize wear debris around loose implants
GABAA receptor subunit regulation after status epilepticus (SE)
Differentially expressed genes (DEGs) related to the cell cycle
Components include genes identified by the cis-signature pathway enrichment () and 3 recently described p53 modifiers and cis-signature genes, RPL26, KDM6B/JMJD3 and BCL2L12, that are not captured by the current annotated gene sets
Genes identified in the phosphatidylinositol and hedgehog signaling pathways
A summary of key steps in TGFβ production and signalling
In normal cells, p53 suppresses glycolysis by inducing expression of TIGAR and inhibiting expression of glycolytic genes such as hexokinase II, phosphoglycerate mutase, and glucose transporter 3 (GLUT3)
Several key factors/signaling pathways in CSCs that are targets of phytochemicals
Leptin signaling: Leptin action is triggered by leptin binding to its long-form receptor (LepRb), which activates the receptor-associated janus associated kinase 2 (JAK2)
Glucocorticoid hormones, secreted as a result of a stressful event, enhance the consolidation of behavioral responses, including memories related to the event
PD-1 signaling dephosphorylates proximal signaling molecules and augments PTEN expression, inhibiting PI3K and AKT activation
Nerve growth factor (NGF) binding to its receptor tyrosine kinase TRKA induces PI3K/AKT signalling, which in turn activates the global translational regulator mTOR
Schematic diagram of the crosstalk between glucose signaling pathways in yeast
Epidermal growth factor receptor family and targeted agents
Primary nodes of signalling activity downstream of T cell receptor (TCR)‚ÄìCD3 and CD28 and inducible T cell co-stimulator (ICOS) co-stimulatory receptors overlap significantly
Schematic representation of ICP10PK-mediated protection of uninfected neurons
(A) In epithelial cells, the major pathway that stimulates host gene exp... (B) In macrophages, insertion of translocons leading to perturbation of...
Potential pathways linking hypoxia to CSCs and EMT in tumor aggressiveness
Therapeutic targets of the androgen receptor signaling pathway
BDNF and its precursor signal locally (curved arrows) as well as over long distances (straight arrows) to modify neuronal morphology
Comparing feedback mechanisms in morphogen signaling
Shown in the middle of the figure is the classical MAPK pathway leading from an extracellular mitogenic stimulus that activates a receptor tyrosine kinase (RTK) in the cell membrane, to RAS, RAF (shown as BRAF-V600E), MEK and ERK
Extracellular signals activate receptor tyrosine kinases (RTKs) in the cell membrane, leading to the activation of RAS and subsequent activation of PI3K
Activation of the MAPK pathway by genetic alterations, such as the BRAFV600E mutation, primarily drives the development of papillary thyroid cancer (PTC) from follicular thyroid cells
The autophagy pathway functions as an intrinsic antiviral defense mechanism by directly engulfing foreign pathogens for lysosomal mediated degradation
Following TCR engagement protein tyrosine kinases (PTKs) such as Lck, phosphorylate the tyrosine residues in the ITAMs in the cytoplasmic tails of CD3Œ∂Œ∂, which serve as docking sites for the Src homology 2 (SH2) domain containing tyrosine kinase ZAP-70
A model of steps in the reverse cholesterol transport pathway
Simplified overview of commonly mutated oncogenes, tumor suppressors, and pathways in endocrine cancer
(A) Isoflavans such as vestitol have been demon... B) Isoflavans and pterocarpans are generally am... (C) A pterocarpan prenyltransferase (GmG4DT), i...
Schematic of Natriuretic Peptide Signaling and Breakdown
Hippo is regulated by multiple signals generated by the physical (matrix stiffness) and biochemical (LPA, S1P, thrombin) environment
The figure depicts the glycolytic pathway from glucose entry into cells through production of pyruvate, which is converted either to lactate or to acetyl coA for entry into the TCA cycle
Illustration of the proposed mechanisms underlying the crosstalk between insulin/IGF1 and IL-17 signaling pathways
Th17/Th22 cells, γŒ¥T cells, and RORγt+ ILCs are major cell populations that co-express transcription factors Ahr and RORγt in the gut
Glucose-6-phosphate dehydrogenase in the pentose phosphate pathway
Role of TRAF6 in RANK Signal Transduction Pathway
Comparison of autophagy pathways in Drosophila and mammals
Activation of TLRs expressed on the cell membrane by a bacterial ligand sets in motion a series of processes that leads to the release of inflammatory chemokines, cytokines and AMPs [,]
RSK isoforms control motility and other aspects of tumor cell invasion and metastasis
The left panel summarizes the fate of glucose through glycolysis, the TCA cycle, the pentose phosphate pathway, and lipid synthesis
This figure briefly summarizes canonical Wnt signaling
While these mutant BRAF inhibitors produce improved overall survival in the patients with BRAF mutations compared to standard treatment options, a major challenge remains: essentially all patients treated with these drugs relapse due to the development of drug resistance, with the median TTP of 7 months for vemurafenib and 5 months for dabrafenib (, )
SIRT1 regulates individual steroid hormone receptors via different mechanisms
Schematic diagram illustrating cardiolipin biosynthetic pathway
Cartoon of the phospholipase Cβ-G protein signaling pathway
Diagrammatic representation of the hedgehog (Hh) signaling pathway
Alcohol metabolism and putative mechanism of alcoholic lung injury
The folate cycle and the methionine comprise of two metabolic pathways that exist independently and thus in modules.The folate cycle: Folate is imported in cells and reduced to tetrahydrofolate (THF).
Diagram of cholesterol biosynthesis pathway showing the chemical structure of some of the intermediates
The Rho GDP–Rho GTP signaling pathway from membrane to the cytosol
MyD-88 dependent TLR signaling pathway: MyD-88 (*) associates with the cytoplasmic domain of TLR, recruiting IRAK1 and IRAK4 to activate TRAF6
After binding to its receptor, IL-33 induces eosinophil activation, as measured by gene transcription and release of several mediators, through the phosphorylation of NFŒ∫B
Schematic overview of multiple feedback loops in the PI3K pathway
Schematic diagram of signal transduction pathway activated by ligand-stimulated FGFRs.Ligand specificity is determined in part by an alternative splicing event in the C-terminal half of the third immunoglobulin domain (bright blue) in which either exon 8 or exon 9 can be used, producing the IIIb and IIIc isoforms, respectively
Proposed mechanism of gremlin regulation of LOXs in TM
Multiple pattern-recognition receptors such as TLRs and NLRs are activated at different stages of bacterial invasion, at the cell surface or in the cytoplasm
Visualization of target genes of CDX1 and CDX2, and the BMP/TGFβ signaling pathway with GenMapp, using cDNA array data (the Hao dataset and the Greenawalt dataset)
Feedback signaling following mTORC1 inhibition
Feedback signaling following PI3K, AKT, or dual mTORC1/2 inhibition
Growth factors, insulin, nutrients and energy status regulate the activation of the PI3K/Akt/mTOR signaling network
Proposed Model for EtOH and PA regulation of mTORC1 and mTORC2 signaling
Bcl-2 inhibition may act directly on tumor cells but may also target the nutrient supply to the tumor by disrupting the blood vessels that form around, and within, the tumor ()
(A) PKCε activation by the selective ψεRACK or the VEGF/VEGFR2 signaling... (B) Blockade with PKCε antagonist or with antibodies against FGF-2 inhib...
Simultaneously targeting both PI3K/Akt and mTOR has the potential to inhibit both upstream and downstream signaling in the pathway
(A) 14-3-3 dimers bind and retain inactive B-Raf protein in the cytosol. (B) In response to exogenous stimuli, tyrosine kinase (TK) receptors act...
When the B-RafV600E oncogene is generated through a point mutation, activation of the MAP kinase pathway becomes constitutive, inducing cells to proliferate indefinitely and initiate tumor formation
In wild-type CD4+ T-cells, upon stimulation with anti-CD3 (and co-stimulatory signal from CD28), the TCR signalsome composed of Lck, ZAP-70, LAT, GADS, SLP76, NCK, ITK, VAV1, PAK and PLCγ 1 is formed, recruiting additional proteins such as PLCγ 1
In the intrinsic pathway, the pro-apoptotic protein Puma is the target of miR-221/222 and is regulated by p53, target of the protein SIRT1, itself regulated by miR-34a
The proposed pathway of 20HE includes activation of a putative membrane bound GPCR
Outline of steps mediating androgen synthesis and metabolism in prostate cancer cells
Pathway based analysis of high ranking composite score genes reveals key signaling pathways associated with PDAC clinical progression
Ingenuity Pathway Analysis (Ingenuity Systems, Inc., Redwood City, CA) of endothelial gene expression
(a) Immune surveillance: astrocytes (AS, blue), microglia (MG, purple) a... (b) Representation of how the levels of key nervous system processes dyn...
Simplified flavonoid biosynthetic pathway showing enzymatic steps specific to the biosynthesis of nutraceutical stilbenes (RS), flavonols (FLS), proanthocyanidins (and lignin [, ], HCT) (LAR and ANR), and anthocyanins (UFGT)
Unfolded protein response and its regulation on cell activities
Diagram representing evolutionary time (large arrow) together with host death pathways targeted by known virus-encoded cell death suppressors
PI3K/AKT/mTOR signaling pathway showing interacting activation and regulatory feedback loops
TNFŒ±-mediated transient IKK activation pathways
Anti-miR (inhibitors of miRNA activity) chemistries are synthesized as antisense oligonucleotides (complementary to the mature miRNA) containing chemical modifications to enhance binding affinity, confer nuclease resistance, facilitate cellular uptake and reduce clearance
Representative pathway depicting proteins and sites identified and quantified (ratio-of-ratios) within the intersection of the Tumor A and B datasets
Classical action of 1,25-dihydroxyvitamin D3 (1,25-D3) is mediated by binding of the vitamin D receptor (VDR) – retinoid X receptor (RXR) – 1,25-D3 complex to Vitamin D Response Elements in the DNA
Schematic model of the TGF-β-induced post-translational modifications of Fli1
The effects of Akt activation status on matrix metalloproteinase 1 (MMP1) gene expression
Ligand binding to epidermal growth factor receptor (EGFR) induces homo-and hetero-dimerization of the receptor, resulting in activation of downstream effectors including the Ras-MAPK (mitogen activated protein kinase), PI3K (phosphatidylinositol 3 kinase)-Akt, and signal transducer and activator of transcription (STAT) pathways that lead to cell proliferation, survival and many other effects associated with carcinogenesis
(a) Recycling of by-products of RNA modificatio... (b) CmP produced during mRnA degradation is rec... (c) The ME-Model uses the canonical glycolytic...
Dual coordinated regulation of CYP7A1 by the FXR-SHP-LRH-1 and FXR-FGF15/19-FGFR4 pathways
The ERK and PI3K signaling networks are shown, with illustrations of feedback loops and cross talk
Chronic low-grade inflammation is associated with increased levels of IL-6, which leads to increased phosphorylation of STAT3, and subsequent increased SOCS3 expression
Potential molecular events associated with tumor suppressor gene product-induced senescence or apoptotic cell death of tissue-resident stem/progenitor cells during chronological aging
Schematic illustration of Rho GTPase signaling pathway
The TNF-Œ± signaling is mediated via TNF-R p55 and TNF-R p75
(A). Tyrosine kinase receptor ligands such as epidermal growth factor (E... (B). The transcription factor Klf5 regulates the expression of early end...
Activation of several receptors on the cell membrane including (but not limited to) ephrin, growth factor receptor, mGluR, and NMDA receptor (NMDAR) leads to inhibition of the hamartin/tuberin/TBC1D7 (TSC1/TSC2) complex
(A) JMJD2A Tudor domain (in red) binds to H4K20me2 in undamaged cells and prevents the damage-associated formation of 53BP1 loci
Reduction of mtDNA content below 70pct disrupts ŒîŒ®m which results in elevated cytosolic Ca2+ and activation of Calcineurin
The essential components of the Cn-mediated retrograde signaling pathway
In addition to apoptosis, AR may also regulate other kinds of cell death
Around stage I in the seminiferous cycle (shown in the upper panel), the MEK/ERK pathway, regulated by an unknown signal, is activated and promotes GDNF expression in Sertoli cells, which leads to activation of MEK/ERK and PI3K/AKT signaling in spermatogonial stem cells via RET/GFRŒ±1 co-receptors
The activation of BIM by cellular stress in normal cells
Mechanisms of cisplatin resistance.Notes: Cisplatin creates DNA adducts and activates the apoptotic pathway, thus killing rapidly dividing cells
= Transporter, ◊ = Enzyme, ∇ = Kinase, ∆ = Phosphatase,   = Transcription regulator, 〇 = Other,   = Complex/group,   = Peptidase
The activation of the NLRP3 inflammasome by its typical stimuli such as ATP, toxin and crystalline reagents involve mitochondria-derived signals such as mROS, mtDNA and cadiolipin
A) Ribosomes consist of a small 40S subunit and a large 60S subunit and catalyze protein synthesis
Apoptosis and necrosis are mediated by death receptor (extrinsic) and mitochondrial (intrinsic) pathways
Human epidermal growth fa ctor receptor 2 (HER2) signal transduction pathways
Signaling pathways interface with Wnt/β-catenin signaling
Consequences of dysregulated Wnt/b-catenin signaling on HIV replication in the CNS
Model of the inverse relationship between Wnt/β-catenin signaling and HIV replication
Basic components of the PI3K/AKT pathway
Apoptosis in mammalian cells is mediated through the intrinsic and extrinsic pathways
Intracellular effects of estrogen are exerted through two main pathways, genomic and non-genomic
Receptor tyrosine kinase (RTK) signaling can lead to the induction of the PI3K/AKT, PKA, and Ras/MAPK pathways
BRAF-specific inhibitors block the RAS-RAF-MEK-ERK signaling pathway in BRAFV600E mutant cells
(A) Serratia marcescens sequesters heme via the HasA hemophore. The HasB... (B) In Staphylococcus aureus, IsdB and IsdH are host hemoglobin receptor...
The data gathered from isotopic tracing of d4-C16:0 FFA labeled cancer cells was compiled into a metabolic pathway map using the KEGG Pathway Database as a guide
(A) Schematic for insulin maturati... (B) Human orthologs of secretory p... (C) Proteins that belong to the se... (D) Heatmap of fifty proteins with...
One putative signaling pathway for cardioprotection initiated by LMW FGF2 via cMyBP-C phosphorylation
Estrogen-induced ER-mediated pathways of vascular relaxation
A. Under normal conditions, insulin binds to the insulin receptor (IR) on endothelial cells and this initiates phosphorylation of insulin receptor substrate 1 and 2 (IRS) and downstream activation of PI3K, Akt and eNOS.
The cholesterol synthesis pathway and protein prenylation
MAPK signaling pathway is upregulated in OSI-906 resistant CRC lines
A schematic representation of the IFN-γ signaling pathway
Overview of the sulfate assimilation pathway in metazoans, yeast, and plants
Multiple feedback loops contribute to commitment and progression through meiotic cell-cycle progression
Proposed cellular mechanisms involved in insulin-stimulated androgen biosynthesis, PCOS-associated defects, free fatty acids-induced insulin resistance and increased androgen production, and PPARγ actions
Rat sarcoma viral oncogene homolog (RAS) activation converts normal keratinocytes to an initiated phenotype through a series of potentially reversible autocrine signals
Divergent roles of myeloid differentiation factor 88 (MyD88) in colon carcinogenesis
The IL-12 family consists of four members: IL-12, IL-23, IL-27 and IL-35
In M-Mac, there is no block to the HIV-1 life cycle and HIV-1 viral DNA is able to integrate into the host genome
Either component proteins or metabolic products from LTA-deficient L. acidophilus are potential antigens that can be recognized by dendritic cells.
A simplified scheme for metabolic proteins that are involved in longevity
TGFβ signaling can occur through multiple pathways
Canonical NF-Œ∫B activation by TCR/CD28 and HTLV1 Tax
Functional annotation table of the components related to the mTOR pathway that have been downregulated (red rectangle) and upregulated (blue rectangle) following P4 treatment based on Nimblegen array data
The model of the signaling pathway mediated by ATM in response to DSBs induced by IR, as proposed by Kitagawa et al
Symbols are colored red when significantly down regulated and green when significantly up-regulated; the intensity of color indicates the magnitude of change, with the scale shown in
Ras-dependent versus Ras-independent extracellular signal-regulated kinase (ERK) signaling
Interaction of a cytokine ligand with the extracellular domains of its cognate receptor initiates the cytokine signaling
(A) Human β-cell insulin resistance in vitro: Nutrient metabolism inhibi... (B) Inhibition of GSK-3 by 1-Akp or LiCl results in activation of Wnt si...
Proposed functions of Spry1 and Spry2 in regulation of eyelid closure
(A) Regarding the Fas/TNFα-mediate apoptosis pathway, fenretinide up-reg... (B) Regarding the RAS/RAF/ERK-medicated survival pathway, fenretinide re...
A basic depiction of the classical view of the PI3K signaling network (black arrows) as well as the novel signaling pathway revealed in the study by Tan et al
MOS-J/POS-1 conditioned media (CMs) induced novel JAKs (JAK1 and JAK2) and PI3-K/Akt signal crosstalk in osteoblastic cells
Under normal conditions, an appropriate level of nmnat transcription is maintained
Canonical WNT/β-catenin signaling and inhibitors
(A) The overall reaction scheme in... (B) Biotinylation of the biotin ca... (C) Production of saturated fatty... (D) Unsaturated fatty acids are sy...
Resveratrol promotes mitochondrial biogenesis and functions through indirect AMPK and SIRT1 activation
Overall PI3K and MAPK-Erk signaling is complex, but can highly influence the balance between cell survival and death
A. Activated EGFR and mTOR signaling promotes SREBP-SCAP complex to move to the Golgi where it undergoes cleavage to form an active nuclear SREBP fragment (N, blue diamonds).
A. Depletion of the C4-demethylating enzymes (SC4MOL and NSDHL) results in accumulation of meiosis activating sterols (MAS) abundantly present in gonads.
Pancreatic cancer initiation pathway for simulation setting (III)
The appearance of ssDNA breaks involves the BER pathway components (APE1, XRCC1 and PARP1) in the process of DNA demethylation
Schematic diagram showing the interaction between NW arenaviruses and host innate immune response
HER2 and PI3K-targeted therapies result in FOXO3a-mediated feedback up-regulation of HER3 and IGF-1R and provide an escape from PI3K pathway inhibition
High nuclear β-catenin confers resistance to AKT inhibition and coordinates with increased nuclear FOXO3a to promote metastases in colon cancer
During chronic lymphocytic choriomeningitis virus (LCMV) infection, virus-specific CD8 T cells are exhausted and B cells are not engaged in effective antiviral responses
a | Nucleotide-binding oligomerization domain protein 2 (NOD2) detects bacterial peptidoglycans and triggers the ubiquitylation of receptor-interacting protein 2 (RIP2), which leads to the activation of the mitogen-activated protein kinase (MAPK) cascade and nuclear factor-Œ∫B (NF-Œ∫B)
Stimulation of the T cell receptor (TCR) leads to the recruitment and activation of protein kinase CŒ∏ (PKCŒ∏), which in turn recruits a protein complex comprising CARMA1, BCL-10 and MALT1
Yang role of PDGF-BB indicated that PDGF-BB-mediated engagement of the activation of TRPC 1 channels resulting in Ca2+ influx transients with subsequent activation of ERK/CREB, but not the Akt/NF-kB pathway, culminating in neuroprotection
A, Complete schematic of VEGFR2 signaling to the ERK MAPK cascade
Conversion of œâ6 and œâ3 series PUFA by metabolic enzymes and interaction with de novo fatty acid synthesis
Main enzymes and G protein-coupled receptors in the cyclooxygenase pathway
A model of the FBXL2- and PTPL1-dependent regulation of the PI(3)K pathway
When Wnt is absent, the destruction complex comprising of Axin, APC and the dual kinases, CKIα and GSK-3β phosphorylate β-catenin and present it to β-TrCP for ubiquitination followed by proteasomal degradation
Targets of immunosuppressive drugs used in solid organ transplantation, according to the 3-signal model of T-cell activation
Increased vulnerability to the depression-like effects of chronic social defeat stress occurs in part via priming of BDNF signaling in the nucleus accumbens (NAc)
Working model for serum deprivation induced mTORC1 inhibition
The death receptors and the extrinsic pathway of apoptosis
A molecular basis for synergistic activation through pairs of coactivation receptors on NK cells
Microorganism-associated molecular patterns (MAMPs) can be recognized as non-self by the host and include compounds such as lipopolysaccharide (LPS), peptidoglycan (PGN), bacterial flagellin and bacterial outer-membrane proteins (Omps)
A. The structure of caspase family proteins and components of DISC and apoptosome.
HIF: Hypoxia inducible factor; HRE: Hypoxia response element; PHD: Prolyl hydroxylases; Ub: Ubiquitin chains; VHL: von Hippel-Lindau tumor suppressor protein
Schematic diagram illustrating central role for ROS and Src in hypoxia-induced pY654-β-catenin/HIF1Œ± formation and tumor EMT
These effects and their significance in RCC are discussed in detail in the text.CRA: Cis-retinoic acid; EMT: Epithelial-to-mesenchymal transition; PFS: Progression-free survival; RCC: Renal cell carcinoma; TSA: Trichostatin A.
(A) PLC/IP3-mediated Ca2+ release signaling pathway in astrocytes. Follo... (B) The astrocytic process together with pre- and post-synaptic regions...
The molecular networks generated from genes differentially expressed in the injured meniscus with age using GeneGo MetaCore are shown
Network pathway analysis integrated the majority of proteins identified as changed on 2DE (), as shown in  but did not include S-methyl-5`thioadenosine phosphorylase, and lamin B1 because of low scoring
Insulin is the major hormone controlling critical energy functions such as glucose and lipid metabolism
Many potential signaling pathways for adiponectin in endothelial cells
Obesity dysregulates multiple aspects of the host microenvironment, including increasing circulating levels of hormones and growth factors, such as insulin, leptin:adiponectin, hepatocyte growth factor (HGF), estrogen and insulin-like growth factor (IGF)-1); vascular regulators such as plasminogen activated inhibitor (PAI)-1 and vascular endothelial growth factor (VEGF); inflammatory factors such as cytokines, chemokines, prostaglandins and free fatty acids
Signaling cross-talk at the various levels of EGFR/HER2 signaling pathways
Cross-talk of EGFR/HER2 signaling with other pathways
An outline of the GPI and GPI-anchored protein biosynthetic pathway
Model of Cav-1 phosphorylation-dependent LPS signaling pathway in mediating lung inflammation in endothelial cells
AMPK is phosphorylated by LKB1 and CaMKKβ, and in turn activates PGC1Œ±
Forkhead box O (FOXO) transcription factors make multiple connections with the cellular signalling network
MDA-7 interferes with tumor promoting pathways
Schematic of PKG regulation of TRPC current and signaling
Invasion gene signaling networks (GSNs) of (A) chronic CNT-exposed and (B) chronic asbestos-exposed MeT5A cells
The cell cycle traverses through the G1-S-G2-M phases tightly controlled by check points between each phase through a set of regulatory proteins, primarily cyclins and kinases
Schematic illustration of the muscarinic acetylcholine receptor subtypes M1–M5
In drug-sensitive cancers (left), the mutant oncogene exerts unilateral control over RAS, MEK/ERK, and PI3K/AKT pathway signaling
Various growth and nutrient signaling pathways are associated with regulation of autophagy
Schematic view of integration of TCR signal transduction with diverse components of the actin polymerization machinery
Analysis with NIH DAVID, Princeton GO term finder and Ingenuity Pathway Analysis yield similar gene enrichments, biological processes and pathways.The high confidence hit list was also analyzed by IPA for biological pathway enrichment
Summary of some kinase-mediated interactions between the purine biosynthetic pathway, its intermediates and energy metabolism in the cell
Multiple hypertrophic signals work through Gq-coupled GPCRs to activate PLC, resulting in the formation of diacylglycerol (DAG) and inositol 1,4,5 trisphosphate (IP3)
(A) The GDP/GTP cycle of Ras is shown. Inactive... (B) The Ras/Raf-1/Erk pathway. This pathway is... (C) Multiplex regulation of, and signaling from...
Reactive oxygen species in cells can be generated by growth factor signaling through activation of the NADPH oxidase NOX1 or through the mitochondria
Schematic representation of proposed DZNep effects on apoptosis regulation in human CCSCs
Physiological regulation of the mTOR pathway
Pathological regulation of the mTOR pathway in neurological disease
Working models of cellular pathways giving rise to phrenic motor facilitation following AIH
(I) Biogenesis and processing. The pol II enzym... (II) The miRNA-binding-mediated mRNA fate. (III) Disruption of miRNA-directed regulation....
Proposed model for the mechanism of SHP-1–mediated inhibition of M
Two different pathways are involved in the synthesis of TAGs: the MAG pathway and G-3-P pathways
TLRs and NODs are pathogen recognition receptors (PRRs) that detect conserved molecules of pathogens
An analogy of a tree with deep roots is used to illustrate several points about chromatin factors implicated in autism
(A) TORC2 signals to Ypk2 to positively regulate de novo synthesis of ceramides at a step that is antagonized by calcineurin
Stress, neurotransmitter release, growth factors and membrane depolarization are among the stimuli that activate intracellular signal transduction pathways that can lead to the activation of the CREB-dependent cascade
A multitude of stimuli and environmental insults including cytokines, stress and growth factors can regulate a considerable number of intracellular processes that critically involve AP-1
A simplified insulin/IGF-1 signaling pathway in cardiac cells and the effects associated with reduced phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling on markers of cardiac aging
The KEGG pathway for Alzheimer’s disease (Kanehisa et al.)
VIP tunes immune and inflammatory response by regulating multiple signaling pathways
Pathogenesis of alcoholic hepatitis with identification of newer therapeutic targets
Redox signaling pathways regulate cardiac hypertrophy
Biological classification of 497 nominated gene candidatesA) Network mapping using Ingenuity Pathway Analysis shows protein-protein interactions among the nominated gene candidates (blue) and known core components (bold red) or regulators of miRNA biogenesis (grey)
Illustration of NF-Œ∫B signaling pathway depicting classical and alternative arms
The transforming growth factor-β (TGFβ)-dependent signalling pathway depends on Type I and Type II serine-threonine kinase receptors and transcription factors known as SMADs
A. Cytokines such as IL-6, or growth factors including EGF and FGF, initiate STAT-3 signal transduction when they bind to their receptors and activate intracellular kinases.
Members of the IL-6 cytokine family bind to a common receptor subunit, gp130, which either homo-or hetero-dimerizes upon ligand binding
Exhibited are the five tiers of novel anti-HIV pharmacological targets in the chemokine/actin signaling pathway
Comparison of in vivo (left) and in vitro (right) signaling support to the intestinal stem cell
The GLI1 target genes converge on a regulatory pathway that suggests roles in cell proliferation, survival and genomic stability
Placement of predicted cancer drivers within specific cellular pathways
In the adherence step, yeast-form cells adhere to the substrate
A model of multiple pathways inducing the switch from mitosis to the endo-cycle
PBK/AKT/FOSLI pathway regulating the invasive trophoblast cell lineage and trophoblast cell-directed uterine spiral artery remodeling
Signal transduction pathways leading to increased HIF-1Œ± protein levels
Insulin receptor substrate 1 (IRS1) and phosphatidylinositol 3-kinases (PI3K) are activated by insulin and/or IGF1 signaling at the insulin receptor level
(A) Summary of KEGG analysis results for genes... (B) and HKc/DR (C) by β 2-fold. Data are grouped into differen...
A wide variety of glycoconjugates such as heparin sulfate proteoglycan (HSPG), chondrotin sulfate proteoglycan (CSPG), N-glycosylated cystatin C, and galectins-1 are involved in signaling pathways inducing proliferation and self-renewal of NSCs
Pharmacological approaches for targeting mitochondrial biogenesis
(A) In Drosophila, gram-negative bacteria binding proteins (GNBPs) and peptidoglycan recognition proteins (PGRPs) have been shown to activate the Toll pathway in the presence of stimulants, such as fungi, yeast, lysine-type peptidoglycan (K-type PGN) and viruses
Synthesis of the C5 isoprenoid precursors IPP and DMAPP
Jak-STAT Signaling Pathway from KEGG (ID: hsa04630) overlaid with log2 fold change values using PathVisio indicating up (red) or downregulation (blue) following ART
Activation of FXR increases hepatic expression of SR-BI, ABCG5/ABCG8, BSEP and Mdr2, and inhibits hepatic expression of CYP7A1 and CYP8B1
The lymphotoxin (LT) pathway organizes multicellular interactions in the lymph node
a|During Citrobacter rodentium infection, the lymphotoxin (LT) pathway is part of an innate feedback loop in which retinoic acid receptor related orphan receptor γt(RORγt) innate lymphoid cells (ILCs)induce interleukin 12(IL 12) and IL 23production by local dendritic cells (DCs) via the LT pathway,
The Yin and Yang of PI3K vs PTEN in the regulation of beta cell proliferation
Hypothesized schematic representation of the intracellular signaling cascade that mediates the mER-induced attenuation of ORL1 receptor- mediated spinal antinociception via rapid non-genomic mechanisms
Signaling pathways for inner ear proliferation and differentiation
ICAM-1-targeted nano- and micro-carriers are both efficiently internalized by cells due to sphingomyelinase (SMase)-dependent generation of ceramide at carrier-binding sites on the plasmalemma, which is associated with CAM-mediated endocytosis (left panel)
Transmembrane signaling of IL-6, which is a major growth factor for MM
Molecular mechanisms involved in leptin receptor signaling in the hypothalamus
In thiscartoon we graphically represent the relationship between critical oncogenic transcriptome networks and the miRNome
Double-stranded DNA (dsDNA) breaks are recognized by the MRE11 complex, which catalyses the activation of ataxia-telangiectasia mutated (ATM) in conjunction with other proteins such as the tat-interactive protein 60 kDa (TIP60; also known as KAT5) acetyltransferase and p53-binding protein 1 (53BP1),
a | Domain structure of the MRE11 complex
Canonical (A) and noncanonical (B) Wnt signaling pathway represented by KEGG analysis
The vasoactive mediators that contribute to the development of pulmonary vascular remodeling and PH can be broadly divided into two major categories: factors affecting vascular tone and factors influencing vessel wall thickening
Binding of EPO to either the homodimeric EPO-receptor (EPOR) complex or the heterotrimeric EPOR-βCR complex first activates Janus tyrosine kinase 2 (Jak2)
Canonical PI3K and MAPK pathway activation determined by reverse phase protein arrays and compared between GBM subclasses: Proneural (P, purple, n=55) and Mesenchymal (M, red, n=45)
Proposed mechanism of TGF-β signaling at the BBB during acute peripheral inflammatory pain
Role of cytokines in Th1 and Th2 differentiation of lymphocytes
Schematic representation of ErbBs/EGFR(s) signaling pathways
The BRAFV600E oncoprotein elicits dramatically an increased kinase activity and activates phospho-ERK1/2
A. In the absence of the Hh ligand, the Hh receptor Patched (Ptch1) inhibits the accumulation of the signal transducer, Smoothened (Smo), on the ciliary membrane.
A. The primary cilium is anchored at the plasma membrane through transitional fibers emanating from the basal body.
Ras proteins function as nucleotide-driven switches that relay extracellular cues to cytoplasmic signalling cascades
(A) Interleukin-2 (IL-2) serves to couple CD8+ T-cell expansion and diff... (B) The establishment of a self-renewing subset of CD8+ T cells within a...
The de novo purine nucleotide biosynthetic pathway including the steps from phosphoribosyl pyrophosphate (PRPP) to IMP is shown
Schematic model of the signalling pathways involved in smooth muscle contraction
The transforming growth factor-β (TGF-β) signalling pathway
Contemporary multistep, two-dimensional model of human breast cancer progression derived from morphological, immunohistochemical, genetic and gene-expression data
Mimicking metabolic mechanisms of epigenetic regulation with small molecules
Exogenous and endogenous genotoxic agents (top) generate a variety of DNA damage, such as single and double strand breaks (SSBs, DSBs), insertions and deletions (indels)
Schematic diagram depicts the underlying mechanism by which LOV protects OLs from cytokine toxicity
Kinetic changes in gene expression of selected components of the Wnt/β-catenin signaling pathway in aging CD8+ T cells
Kinetic changes in gene expression of selected components of Th2 responses
The death receptor pathway (left) is initiated by the binding of a ligand (Eg: FasL) to its receptor Fas, which results in the sequential recruitment of FADD and pro-caspase-8
Long-chain fatty acids enter the cell and are activated by acyl-CoA synthetases to form acyl-CoAs, which are then esterified to glycerol-3-phosphate to form LPA by glycerol-3-phosphate acyltransferase (GPAT)
(Top pathway) JAK/STAT signaling specifies trachea by activating expression of early tracheal genes, including two transcription factors, Trh and Vvl
Schematic diagram of Pak activation by the small GTPases Rac and Cdc42
(A) Ang II-mediated stimulation of AT1R leads t... (B) AT1R stimulation mediates hypertrophy via d... (C) Activation of AT1R leads to Gαq protein-med...
Etoposide promotes p53 translocation from the cytoplasm to the nucleus to promote transcription of target genes involved in cell death
(A) In yeast, mitotic exit requires Nud1 phosph... (B) In mammalian cells, Cdk1–cyclinB phosphoryl... (C) A third example of phosphorylation-dependen...
P. gingivalis gingipains (Kgp, HRgpA, RgpB) inhibit the classical, lectin, and alternative pathways of complement activation by degrading the central complement component C3.
Bile acids (CA and CDCA), synthetic FXR agonists (GW4064, INT-747 and WAY-362450) and a dual FXR/TGR5 agonist (INT-767) activate hepatic FXR, resulting in modulation of hepatic and plasma lipid homeostasis
(A) A broad range of dynamics are transmitted through the Ras/MAPK module to Erk activation (representative timecourses shown in blue) and are differentially sensed by “fast” and “slow” downstream decoding modules (representative timecourses shown in green)
Models of RB/E2F and RNA processing control
Key organelles and proteins involved in cellular Cu homeostasis
Ligand binding to the IFNAR and transphosphorylation of TYK2 & JAK1 can cause recruitment and phosphorylation of STAT proteins other than STAT1 and STAT2 (e.g.
Activation of GŒ±s/olf proteins on D1-like receptors stimulates adenylate cyclase ()
A representative MLL fusion protein complex is shown that recruits a transcriptional activation complex
NFAT proteins activate an anergy-inducing program of gene expression
(A) Pyramidal cells emit the first axons in cerebral circuits. They exhi... (B) Later-arriving GABAergic axons do not express DAGLs in their growth...
Figure shows scheme of VEGF receptor signaling pathway in CLL as well as aspects of pathway targeted by bevacizumab, AZD2171, and sunitinib malate
The inflammatory cytokine Interleukin 6 (IL-6) plays an important role in hepatocarcinogenesis through the modulation of STAT3 pathway, MAPK route and cell cycle progression
Activating components upstream of YAP/TAZ are in green, inhibitory components are in red, and putative YAP/TAZ inhibitors are in gray box
a) Digrammatic representation of follicle growth from the non-proliferating pool of primordial follicles
The intersection of glucose metabolism and NAD salvage
Wnt signaling pathway represented by KEGG analysis
Diagram of known egg activation pathways in Drosophila, Xenopus, and mouse
Right side shows the MAPK pathway; left side shows the PI3K-AKT-MTOR pathway
A. Activation of the non-canonical inflammasome after phagosomal lysis and leaking of bacterial components.
Demonstrated signaling connections are presented as black arrows, pharmacological activators are connected to their targets with green arrows, and pharmacological inhibitors are connected to their targets by red blunt-ended arrows
The mating response pathway is initiated when the pheromone α factor binds to the GPCR Ste2 at the plasma membrane
A) Akt is activated by extracellular signals that activate PI3K
Schematic of the HER4 signaling model, highlighting the two divergent pathways: PI3K/AKT and JAK2/STAT5a
Regulation and effectors of the mTOR signaling pathway
Holo-Tf binds TfR1 on the cell surface; the complex internalizes in endosomes, where acidification promotes iron release from Tf
The Toll/IL-1 receptor (TIR) domain-containing adaptors have one of two roles
Activation of ABL kinases downstream of hyperactive RTKs, chemokine receptors and Src kinases, or in response to oxidative stress promotes cancer cell invasion by direct or indirect activation of actin regulatory proteins such as cortactin, N-WASP, Abl interactor 1 (Abi1), WAVE, CrkL, HEF1/NEDD9, and the Rac GTPase, , -,
Left panel: MUC4-dependent mechanisms involving either decrease of hCNT1 nucleoside transporter expression via the NF-Œ∫B pathway or modification of the Bax/BclXL ratio (up-regulation of BclXL and down-regulation of Bax expression)
Three major pathways are critical for regulating basal and stimuli-induced hepcidin expression
Potential molecular signaling pathways mediated by MET receptor tyrosine kinase in neurons
Canonical signal transduction cascades and mood stabilizer targets in bipolar disorder
Neuroprotective/apoptotic intracellular cascades at baseline and as mitigated by mood stabilizers in BD
Signaling abnormalities and impairment of neurotrophic cascades that underlie the neurobiological basis of bipolar disorder
A scheme for illustrating the effect of Naproxen on the regulation of cell cycle and apoptosis mediated through the inhibition of the PI3-K signaling pathway
Schematic illustration of the initial enzyme mediated steps in the two major pathways of O-Man glycan elongation
The Toll, Imd and JAK-STAT immune signaling pathways
The role of endogenous fatty acid metabolism in the control of hepatic gene transcription
A. Regulation of Wnt signaling pathway in normal cells.
MG53-mediated negative feedback regulation of skeletal myogenesis
Hypothetic mechanisms of cancer therapy-induced HSC senescence and LT-BM injury and potential strategies for therapeutic intervention
Hepcidin expression is increased in response to elevated iron and decreased due to ineffective erythropoiesis, such as is found in β-thalassemia intermedia
(A) Genetic ablation of the Hfe protein (Hfe−/−... (B) greatly diminishes tissue iron loading and... (C) initiates hepcidin production through stimu...
Molecular mechanisms in Carney complex (CNC) and McCune-Albright syndrome (MAS): Receptor activation (ligand binding) makes GsŒ± to exchange GDP to GTP, GsŒ± is then freed from the β-γ dimer and activates adenyl cyclase (AC)
A) ACTH binds to its specific seven-domain transmembrane receptors (MC2R), leading to activation the Gas protein, which will activate adenyl cyclase (AC) and, therefore, cAMP production
A) In the absence of the ligand, cytosolic β-catenin is continuosly phosphorilated by the «destruction complex»
Progestins diffuse through the plasma membrane and bind PR causing rapid SUMOylation on Lys388 on a subset of receptors resulting in transcriptional repression at many cancer relevant genes
TLR2 and TLR4 are present on the cell surface and recognize viral proteins
A. Insulin signals through at least two pathways to mobilize GLUT4 to the plasma membrane.
A simplified scheme of kidney development (top row) and acute kidney injury (AKI) induced regeneration (circle)
BMP signaling is initiated by ligand binding to membrane associated type I (ALK3/6) and type II (BMPRII) receptors
Upon microbial infection, pattern recognition receptors (TLRs and RLRs) recognize pathogen products to trigger downstream signaling pathways to induce IFN-I and pro-inflammatory cytokines
Shown is a summary of published studies (; , ; ; ) and results herein
A) Neurons in the hippocampus play critical roles in learning and memory... B) Signaling pathways by which glutamate, BDNF, insulin and glucagon-lik...
MUC4 stabilizes HER2, leading to the PI3K-dependent activation of AKT and activated AKT enhances the phosphorylation of the NF-Œ∫B p65 subunit
(a) RPM, (b) TGEM, (c) BMDM, and (d) RAW macrophages express different proportions of TBXS, PGIS, PGDS (H-PGDS), and induced PGES (mPGES-1) that result in a close correlation with metabolite proportions, but only in cells that lack PGIS
Glucose-derived metabolites can be used to generate pyruvate or to supply precursors for the pentose phosphate pathway and de novo serine synthesis
The glycerol 3-phosphate (or phosphatidic acid) pathway represents the de novo lipogenesis route in the synthesis of triglycerides (TAG) and phospholipids
Testosterone exerts slower genomic actions by diffusing through the plasma membrane and binding with intracellular androgen receptors to form complexes
Proposed signaling pathway for PCB detoxification in vivo
Colorectal carcinogenesis progresses by at least two well-recognized pathways
Right hand side of the diagram (Wnt-Frizzled signaling) shows that when epithelial cells shift below the lens equator they initiate fiber differentiation in response to FGF in the posterior segment
The proposed model for the signaling events in mature, human oligodendrocytes in response to B
Potential cellular response pathways of RPE cells upon AGE stimulation
Molecular pathways regulated by PGE2 that are inhibited by aspirin
Blood-cell development progresses from a hematopoietic stem cell (HSC) through sequential stages of differentiation, ultimately giving rise to the individual mature cell types found in the circulation, including platelets, erythrocytes, monocytes, neutrophils, eosinophils, basophils, T cells, natural killer (NK) cells, and B cells
Shear stress sensors transduce signals leading to ERK1/2 phosphorylation and Thr38 phosphorylation of Ets-1
This network was identified by Ingenuity Pathway Analysis with an IPA score of 27 (Network 3, )
Nucleotides are sensed by TLRs in endolysosomes in order to allow for the efficient discrimination between pathogen-associated and self-derived nucleic acids
Regulation of G protein-mediated signaling by RGS2 in the heart
Two major signaling pathways activated by HBV and HCV in hepatocarcinogenesis
When melanocortin peptide ligands bind to MCRs, which are prototypical G protein coupled receptors, they causes a conformational change in the MCR, which allows it to act as a guanine nucleotide exchange factor
STAT-5 has important roles in cell proliferation, apoptosis and differentiation
(A) Illustration shows RET gene structure with 20 exons (solid boxes) an... (B) Schematic shows RET signaling components using RET 51 as an example....
(1) In young hepatocyte specific TAK1-deficient (TAK1ŒîHep) mice, NF-Œ∫B activation is inhibited, while TGF-β-induced Smad2/3 activation is enhanced, which promotes hepatocyte death and compensatory proliferation
FAK and tumor microenvironment Cancer cells are surrounded by cancer cell niche or tumor microenvironment components, such as extracellular matrix, endothelial cells, blood vessels; and immune cells, playing a significant role in inflammation
Ack1 signaling pathway in normal and cancerous cells
Pathway for MEK5/ERK5- mediated cell survival: When cell stress occurs, a nonphosphorylated form of Bad translocates to the mitochondria to induce cytochrome c release and a nonphosphorylated Foxo3a translocates to the nucleus to induces transcription of FasL receptor
Proposed MEK5 regulation in breast cancer: Similarly to MEK5/ERK5 pathway activation in physiologically healthy tissue, activation may occur through extracellular stressors, mitogens or cytokine activation to promote survival, anti-apoptotic signaling and proliferation of cancer cells
Activating mutations in β-catenin (CTNNB1) or mutations in members of its destruction complex (AXIN1; CSNK1A1) correlate with sensitivity to navitoclax (A)
Cell non-autonomous mechanisms that regulate cortical development consist of cell signaling events initiated by extracellular factors in the cytoplasm or through cell-cell interaction
Proposed signaling pathway of EGb 761-induced neuroprotection and neurogenesis
The major components of the NF-κB and p38 MAPK signaling pathways in response to IL-1 are diagrammed
Chemotherapy, radiation and other insults can initiate apoptosis through the mitochondrial intrinsic pathway
Schematic diagram of potential crosstalk signaling pathway between PACAP and BDNF leading to neuroprotection; 1st, 2nd, and 3rd represent the three mechanisms leading to neuroprotection; arrow up—activation; arrow down—inhibition; striped line—plasma membrane
Glucose and glutamine metabolism is altered by oncogenic K-Ras
The phosphoinositide-3-kinase (PI3K)/Akt pathway is highly active in many tumor cells, including medullary thyroid cancer
Major components of the TGF-ß signaling pathway
A. GCs especially when added in the presence of insulin, mimicking the fed state, induce the expression of genes involved in lipid uptake (LPL), TG synthesis (LIPIN, AGPAT, DGAT1) and de novo lipogenesis (ACC, FAS).
Schematic overview of the mTOR signaling pathway with the most important factors and their action
Schematic overview of the mTOR signaling pathway with the target position of drugs
ErbB4 agonists and antagonists stimulate the formation of EGFR–ErbB4 heterodimers that possess distinct conformations
NF-Œ∫B signaling pathways in osteoclast lineage cells
IAP antagonists and NF-Œ∫B signaling in osteoclast lineage cells
Simplified model of signaling pathways regulating protein synthesis and degradation
Current and future potential therapeutic targets in TNBC include: modulation of homologous recombination repair mechanism deficiency (platinum alkylators, PARP inhibitors [yellow], Chk1/2 inhibitors [blue]), modulation of p53 family signaling (PI3K/Akt/mTOR inhibitors [red], Chk1/2 inhibitors, Wee1 inhibitors [blue]), modulation of androgen receptor (PI3K/Akt/mTOR inhibitors [red], AR antagonists [dark green]), modulation of MAPK/MEK pathway (MEK inhibitors [light green])
The relationships between the cellular signal pathways in HAdV-36 infected human muscle cells
Reconfiguration of a signaling network upon drug treatment
A, General schematic of the classical view of cell surface receptor-mediated intracellular signaling
Signaling pathways that can be inhibited to increase the radiation response of tumors
In fibroblasts, TGF-ß binding to its receptors causes Smad2/3 activation, recruitment of transcriptional coactivator p300 and enhanced collagen gene transcription
Schematic diagram of hypothetical mechanisms of tolerance within the TLR4 pathway
Model of bile duct regeneration in different disease conditions
Transcriptional regulation of Wnt pathway genes by Pitx2 leads to Daam2 activation
Immunopathogenesis of inflammatory bowel disease (IBD)
A role for the Th17 pathway in a subset of asthma patients?
Mechanisms by which Th17 and Th22 pathways contribute to psoriasis and atopic dermatitis
We previously demonstrated that GSH depletion is required for the execution phase of apoptosis (1) []
RGS proteins in the regulation of GPCR, PTH, and Wnt signaling pathways during bone remodeling
Schematic representation of Cl‚àí channels in cardiac myocytes
Schematic description of FGF15/19-mediated repression of Cyp27 and Cyp7a1 in cholangiocytes and hepatocytes
Multiple factors within tumors promote immune tolerance and curb the anti-tumor immune response
In the cytoplasm, AEG-1/MTDH/LYRIC has been proposed to regulate mRNA stability, loading in the polysome, and protein translation, putatively by interacting with distinct mRNA sequences (; )
1A: Base excision repair (BER) pathway targets DNA damaged during replication or by environmental agents
A) Pathogen recognition receptors RIG-I and TLR3 detect HCV ds RNA and a... B) HCV attenuates innate immune responses at the multiple levels. NS3/4A...
(a) The initial events elicited upon binding of ICAM-1-targeted carriers... (b) The signaling cascade governing this pathway is shown, including act...
Note that hypothermia therapy may reduce neurological injury through cellular and molecular regulation by decreasing metabolism and energy consumption, attenuating mitochondrial injury, inhibiting inflammatory mediators; decreasing MMPs proteolytic activity, inhibiting the FasL signaling pathway protecting the blood brain barrier, increasing HSP70 expression, inactivating NF-Œ∫B and downstream transcriptional targets, limiting calcium influx through AMPA, decreasing excitotoxicity, etc
Note that IPC/HPC may block the biochemical cascades that cause brain injury following cerebral ischemia by improving CBF through PKC activation and adenosine transporter inhibition, inhibiting apoptosis through the PI3-kinase/Akt pathway, protecting BBB by diminishing MMP-9 and increasing SphK2, stimulating DOR signaling and thus regulating survival and death signals, inhibiting glutamate toxicity and maintaining ionic homeostasis, attenuating acute inflammatory processes though the PKC/ERK pathway, inhibiting mitochondrial cell death signaling through the AKT/PKC/MAPK/ERK pathway increasing autophagy
A–C | Inhibition of apoptosis and anoikis by autophagy
(A) Many negative feedback loops in mTOR signaling. When mTORC1 is activ... (B) Rapamycin relieves negative feedback loops and promotes activation o...
Schematic showing actin cytoskeleton signaling pathways in adult hippocampal spines (see []) and the proposed mechanisms by which the glucocorticoid receptor (GR) affects actin assembly and stabilization
The intuitive web-based analytical tool Ingenuity Pathway Analysis (IPA) was used to generate plausible colorectal cancer metastasis signaling networks
(A) pDC are recruited into the tumor microenvironment via multiple recep... (B) CD19+ pDC in tumor-draining LN (TDLN) produce high levels of IDO whi...
Overview of the genes involved in the WNT signaling pathway
Roles of SOCS in feedback regulation of innate immunity
Copper, taken up via CTR1 (red) is transferred to chaperones ATOX1, CCS and COX17, which ferry it (black dash arrows) to ATP7A/B (blue) in the Golgi, to Cu–Zn superoxide dismutase (magenta) in the cytosol and to cytochrome c oxidase (green) in the mitochondria, respectively
Recent studies characterize a two-step mechanism for the processing of double-strand breaks (DSBs) at the 5′ ends to expose the 3′ single-stranded DNA (ssDNA) overhangs
(A) Hepcidin regulation by extracellular iron. The BMP/Smad pathway is c... (B) Hepcidin regulation by inflammation. IL-6 and other cytokines (e.g....
A. In normal melanocytes, cyclic AMP pathway activation promotes PKA-mediated inhibition of CRAF.
Melanoma cells with mutations in the RAS/MAPK signaling pathway are sensitive to combine therapy of leucine deprivation and inhibition of autophagy
MiRNA regulation of skin fibrosis in epithelial and fibroblast cells
Brief priming with LPS induces ERK1 phosphorylation that likely induces changes in either the localization or interaction of ASC with an NLR component of the inflammasome
Glucose is transported into the cardiomyocyte by glucose transporters (GLUT)
4EBP1, eukaryotic initiation factor 4E-binding protein 1; EGF, epidermal growth factor; EGFR, EGF receptor; ERK, extracellular signal-related kinase; HER2, human epidermal growth factor receptor; INPP4B, inositol polyphosphate-4-phosphatase; IRS-1, insulin receptor substrate 1; MEK, mitogen-activated protein/ERK kinase; mTORC, mammalian target of rapamycin complex; PI3K, phosphatidylinositol 3-kinase; PIP, phosphatidylinositol 3-bisphosphate; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol 3,4,5-bisphosphate; PTEN, phosphatase and tensin homolog; S6K, ribosomal protein S6 kinase
a | MicroRNAs are important regulators of effector T cell differentiation, including T cell activation, acquisition of effector functions such as cytokine production, and T cell proliferation (top panel)
a | Treg-specific miRNA expression is required to restrain effector T cell responses
A model representing our current understanding of the maintenance of the pluripotent state in mouse pluripotent stem cells
Model for the role of sphingosine (SPH) in controlling the transactivation potential of steroidogenic factor 1 (SF-1)
Insulin signaling pathways that control gluconeogenesis
Notch signaling pathway and agents in clinical development
Schematic of PGD2 pathway in alopeciaDepicted is our current understanding of prostaglandin synthesis and changes in alopecia
Paradoxical activation of the MAPK/ERK pathway in tumours treated with RAF inhibitors
MAPK signalling cooperates with loss of APC to promote adenoma development
Red arrows denote the classical Aβ-tau cascade (Pathway 1)
Diagram of putative mDA differentiation pathway based on this and other studies
β-Catenin is a multifunctional protein that localizes at cell-cell contacts, the nucleus, cytosol and centrosomes
(A) HER2 antibodies and anti-HER2 vaccines, (B) antibody–drug conjugate, (C) tyrosine kinase inhibitors, (D) PI3K/AKT/mTOR pathway inhibitors, (E) monoclonal antibodies and small-molecule inhibitors, (F) Clostridium perfringens toxin-based therapeutic approaches and (G) CDK inhibitors and curcumin
Low concentration S1P enhances invasion through activation of uPA and MMP2 via Gi and Rac
(a) The protein cargos are transported from the Golgi to the basal body... (b) The primary cilium modulates several signal transduction pathways. S...
Diagram illustrating the signaling pathways involved in the specification of the PPR, and the subsequent step-wise induction of sensory placodes with distinct identities
Copper is passed (green arrows) to cuproproteins (dark green circles), including metallothioneins Crs5 and Cup1, in for example Saccharomyces cerevisiae, by copper metallochaperones (pale green circles, or ovals if membrane associated)
A. RB mediated repression of the activator E2Fs is relieved after cells pass the restriction point.
Various signaling cascades can affect mitochondrial physiology, mediate mitochondrial radical formation or are connected to apoptotic signaling
Dendritic cells initiate T cell immunity in the lymph nodes
Through a multiple-step process, growth factors stimulate AKT, which in turn phosphorylates and inhibits the tuberous sclerosis complex (TSC; comprising TSC1 and TSC2)
In one scenario (right), IL-15 binds to its high affinity IL-15RŒ± expressed on an antigen-presenting cell and in turn is presented in trans to the IL-2/15Rβγ heterodimer
A: Simplified pathway map of CCN1 and CCN2-dependent outside-in signalin... B: Interaction of CCN1 and CCN2 proteins via their constituent domains w...
Estrogen promotes actin polymerization in CA1 dendritic spines
As discussed in the main text, BDNF signaling via TrkB vs. p75NTR is complex but elegant, allowing for a diversity of signaling mechanisms and cellular effects that are cell type- and context-dependent.
HDACs and associated corepressors (the molecular brake pads) act to suppress gene expression necessary for long-term memory formation and maintenance ()
The role of genes identified in GWAS of Phase 1+2 AA subjects using a case-control model in the canonical pathway “calcium signaling.” The gene or gene families with a significant association result are shown in orange
Growth factor binding to receptor tyrosine kinases activates PI3K (phosphatidylinositol 3-kinase) and PTEN suppresses signaling through this pathway
The PI3K-mTOR pathway and possible mechanism of HSC depletion and leukemia initiation
Schematic of canonical BMP signaling pathway
Receptor tyrosine kinase trafficking may affect signal transduction
Soluble asTF and membrane-bound flTF induces membrane receptor-mediated signaling
This diagram shows a highly simplified scheme of the signaling pathway leading from PI3K to AKT to mTOR
(A) The TORC1-TORC2 network and key feedback mechanisms. The mTOR serine... (B) Redundancy and feedback between the RAS-RAF-MEK-ERK and PI3K/AKT/mTO...
The Dashed line signifies that rapamycin inhibits mTORC2 in specific cell types or after prolonged treatment
mTORC1 inhibition is protective during ischemia through the upregulation of adaptive mechanisms
Schematic diagram of myocilin signaling in cell migration
Pathways for (A) Maturity Onset Diabetes of the Young (hsa04950), (B) type 2 diabetes (hsa04930), and (C) Notch signaling pathway (hsa04330); adapted from Kanehisa, et al []
Pathway analysis and molecular interactions of focus genes AKT, CTNNB1, GAB2, and SERPINE1 (hightlighted in pink)
A variety of external inputs can disrupt Foxp3+ Treg function
Involvement of Rac in NADPH oxidase activation and superoxide production and cell migration
PAMPs recognition through TLR-4 leads to the activation of NFŒ∫B, which is translocated to the nucleus and moderately enhances the iNOS promoter activity
(A) Metastatic traits acquired by a quantitative gain in pathway output
Many of the known traits that promote metastatic seeding involve gene products (red) that the cancer cells express to amplify their own responsiveness to vital stromal cues
The figure illustrates the mTOR signaling pathway in mammals
1. IL-4 and IL-13, upon binding to their common receptor IL-4RŒ± phosphorylate STAT6 to begin the induction of AAMac polarization.
mTORC1 is a component of mTOR that is directly inhibited by rapamycin and rapamycin derivatives like everolimus
Inflammatory cytokine-associated idiosyncratic drug hepatotoxicity as a “network toxicity”
(A) Atherogenesis is influenced by the LT-pathw... (B) Hepatic lipid homeostasis can be regulated... (C) Weight gain and glucose intolerance are inf...
NRG1 signalling and neurite formation mediators
Inhibition of myomiRs by TWEAK inhibits myogenesis
Binding of trimeric TWEAK to Fn14 receptor leads to the recruitment of cIAPs and various TRAFs resulting in the activation of multiple downstream signaling cascades
Acetyl-CoA and acetoacetyl-CoA catalyzed by 3-hydroxy-3-methylglutaryl CoA synthase (HMGS) are converted to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA), which is then converted to mevalonate through the action of HMG-CoA reductase (HMGR) and the cofactor NADPH
The Wnt pathway and its interactions with other pathways in bone
The role of the canonical Wnt, Ihh, Bmp and PTH/PTHrP signaling pathways in regulating the differentiation of mesenchymal precursors
Death receptor signaling and programmed necrosis
Simplified overview of the receptor tyrosine kinase (RTK)-RAS and RAS-related RHEB signaling pathways
Growth Factor (GF) ligands will induce Growth Factor Receptor (GFR) signaling, resulting in phosphorylation of PR at ser294 by the MAPK pathway, leading to both ligand-independent receptor activation and induction of proteosome-mediated PR degradation, and/or may lead to direct suppression of PR transcription by the Akt/mTor pathway (with a resultant decrease in PR protein expression)
Multiple mechanisms of acquired BRAF inhibitor resistance have been identified
A typical contraction in a mammalian cardiomyocyte is initiated by Ca2+ entry into the cytosol via L-type Ca2+ channels on the sarcolemma
APP undergoes cleavage via two different pathways (A)
In carcinogen-associated HNSCC, chronic exposure to reactive oxygen species and repeated DNA damage lead to NF-Œ∫B activation
Extracellular signals such as EGF, TNF, IL-1, and other growth factors (1) bind to their respective receptors (2), and induce phosphorylation cascades through signaling pathways, such as PI3K-Akt-mTOR, MAPK, and IKK (3)
IL-22 binds as a homodimer at a receptor complex composed of the IL-10R2 and the IL-22R1
Microbial pathogens and their components initiate the innate immune response through activation of multiple signaling pathways, most importantly the TLR-NF-κB axis, driving the production of multiple pro-inflammatory cytokines
On the right, signaling pathways involved in mediating cavernosal smooth muscle cell (CSMC) relaxation
Glucose metabolism in euglycemia vs. hyperglycemia under normoxic conditions.
The hyperglycemia-induced intracellular AGE precursors, such as MGO, induce pathological consequences in four routes, 1) direct intracellular glycation of proteins, including proteins involved in the regulation of gene transcription, such as NF-Œ∫B, 2) inhibiting enzymes responsible for protein degradation, such as proteasomal (including ubiquitin) and lysosomal systems, 3) the intracellular AGEs precursors can diffusing out of the cell and modify nearby cells (even the same cell itself), extracellular matrix, such as Bruch‚Äôs membrane and choroidal capillary membranes, and 4) the intracellular AGEs precursors diffusing out of the cell to modify circulating proteins in the blood, which in turn activate RAGE on pro-inflammatory cells or CECs, thereby causing the production of inflammatory cytokines and/or growth factors
Under hyperglycemia, AR reduces glucose to sorbitol (a polyol or sugar alcohol), which is later oxidized to fructose
The pathogenic consequences of hyperglycemic PKC through activating transcription factors for a wide range of proteins, including cytokines
The hyperglycemic hexosamine pathway starting from the glycolytic intermediate, F-6-P, which is converted by GFAT to glucosamine-6-P and eventually to UDPGlcNAc, an O-linked GlcNAc
bFGF: Basic fibroblast growth factor; PDGF: Platelet-derived growth factor; PDGFR: Platelet-derived growth factor receptor
Signaling networks for brain, lung, and bone metastases of breast cancer
Statins, bisphosphonates, FTIs and GGTIs are different classes of drugs which have various inhibitory effects on the MVA pathway
Upon binding B7-1 or B7-2, CTLA-4 recruits the phosphatases SHP2 and PP2A via the YVKM motif in its cytoplasmic domain
Reactive oxygen species (ROS) initiate a common pathway by which hematopoietic stem cells abandon self-renewal and exit quiescence in favor of differentiation
The process of AGE damage and RAGE activation offer multiple approaches for preventing neuronal damage, from preventing AGE formation to blocking downstream signaling cascades
A: recognition of self-antigen (Ag) by TCR in the absence of co-stimulat... B: balanced TCR/CD28 signaling activates both AP-1 and NFAT to induce IL...
Activation of the Bone Morphogenetic Pathway (BMP) occurs at a gradient that is higher in the villi and lower in the crypts
Growth factor mediated activation (EGF) of a receptor tyrosine kinase (EGFR) leads to downstream pathway signaling along the RAS-RAF-MEK-MAPK and PI3K-AKT-mTOR pathways
The canonical miRNA biogenesis pathway and miR-RISC activity are schematically represented
Cap-dependent and elongation translational control by GNRH
Model depicting the proposed mechanism for inhibition of BMP signaling by CaN
A.) Similar to bacterial chemotaxis, an adaptation module may be present early in the signaling pathway.
The Bayesian Brain Immune and Microglia Module
A schematic illustration of the N-linked glycan pathway with the relevant glycosylation enzymes is shown
Ciliary-vesicle-dependent steps of ciliogenesis, and modular organization and mechanism of the IFT machinery
Model depicting ciliary cargo trafficking pathways
Schematic of the IRS-1→PI3K→Akt insulin signaling pathway
Schematic summary of hippocampal formation alterations in the IR→IRS-1→PI3K→Akt→mTOR signaling pathway of AD dementia cases versus age- and gender-matched controls
Pathways leading from ssDNA-bound RPA to the recruitment of an error-prone polymerase η, ι, κ or Rev1 for bypass of a potential template lesion
DHA reduces the production of the β-amyloid peptides (Aβ) from amyloid precursor protein (APP) by increasing expression of the anti-amyloidogenic chaperone LR11, a protein which prevents APP from reaching the proteolytic secretases that cut Aβ from APP
As reviewed in  and , DHA has multiple-reported neuroprotective and anti-Aβ effects
Schematic depicting the selective assembly of the necrosome/necroptosome under I/R or inflammatory (Infl.)
Wnt/β-catenin pathway genes that were significantly differentially expressed in the colon tumor tissue samples are indicated by red or green shading (red for up-regulated and green for down-regulated)
Activation of the Smad1 pathway requires cooperation between two ligands, transforming growth factor β (TGF-β) and CCN2, signaling through their cognate receptors
Most IGF-1 within the extracellular intravascular compartment is sequestered in a binary complex with IGFBP-3 or in a ternary complex with IGFBP-3 and an ALS
Akt is a serine-threonine kinase that is part of the PI3K signaling pathway
Genes involved in the TGF beta signaling pathway after 5 days
Oncogene Induced Senescence (OIS) can initially be driven an activating mutation in Ras oncogene and eventual amplification of activated Ras signal
Black arrows indicate the signalling pathway necessary for establishment of planar cell polarity (PCP)
TGF-β family signaling for Müllerian duct regression
Bacterial effectors that target and manipulate the innate immune and inflammatory pathways
Network analysis showed pathways associated with the NARP21 gene signature genes (21 genes) derived from NF-Œ∫B activated androgen depleted mouse prostate
Model of the ERK1/2 MAPK signaling network controlled by receptor tyrosine kinases and Ras
Phosphorylation of the activation loop serines on MEK1 and 2 decreases affinity for allosteric inhibitors such as trametinib and selumetinib
a | Normal transforming growth factor-β (TGFβ) signalling in TGFβ-responsive cells (blue cells) feeds through the type 2 TGFβ receptor (TGFBR2) to activate downstream signalling targets
Schematic diagram of mechanism of white matter damage in SHR-SP
The corresponding HUGO gene identifiers for each node are given in the legend on the left hand-side
AR antagonists have been shown to inhibit cell proliferation in A) TNBC AR+ and B) ER-HER2+AR+ breast cancer subtypes, the latter through its interaction with the HER2/3, Wnt/β-Catenin and c-MYC pathways
p53 is able to transcriptionally repress glucose transporters GLUT1 and GLUT4 along with the insulin receptor (IR) to inhibit cellular glucose uptake in to the cell
a | Transforming growth factor-β (TGFβ) family ligands signal by assembling a hetero-tetrameric receptor complex with two type I (which are the main signal propagators) receptor components (shown in light grey) and two type II (which are activators) components (shown in dark grey)
Conservation of host cells and pathogen categories in zebrafish and mammalian infection by eukaryotes
The JAK-STAT5 signaling pathway is activated by GH, PRL, and GM-CSF, and it regulates the development and/or function of preadipocytes, adipocytes, and macrophages in adipose tissue
This figure illustrates the known AJ and TJ proteins expressed by the human BNB in vitro, and their accessory or regulatory proteins and their membrane localization guided by knowledge of other restrictive barrier forming endothelial cells
Schematic representation of signaling pathways modulated by PKD1 in cancer
HIV induction by PKC activators and HDAC and BET inhibitors: NFŒ∫B is sequestered in the cytoplasm by IŒ∫B
Signal transduction by prostaglandin receptor EP2
Mitochondrial and metabolic checkpoints of T-cell activation and apoptosis signals
Of the several different complexes that are thought to be important for MLL-leukemogenesis, the Dot1l complex (a), the SEC complex (b) and the Brd4 complex (c) are depicted
MAPK pathway signaling in malignant melanoma leads to phosphorylation and activation of RAS, RAF, MEK, and ERK, a process that ultimately regulates the cell cycle, differentiation, and apoptosis
The schematic shows two possible signaling pathways that can be triggered by nerve growth factor (NGF) binding
Insulin activates SREBP-1 through multiple mechanisms
EPEC1 and EHEC use different mechanisms of Tir activated signaling cascades that converge on common host actin nucleation factors, N-WASP and Arp2/3 to form actin pedestals
Active (farnesylated, membrane-bound and GTP-bound) RAS modulates a number of signalling pathways
MicroRNAs (miRNAs) regulate distinct aspects of the germinal center (GC) response
Nucleic acids encounter TLRs in endosomes after uptake from the extracellular milieu
(A,B) Scanning electron micrograph of a wild type (A) or GMR-upd (B) adult eye
Bid can be activated by multiple proteases in response to a variety of pathophysiological signals
Purinergic autoregulation model of mechanosensitivity in human ECs
Signaling pathway initiated by Edn1-induced Ednra signaling
Model of complement activation and effector functions
Glucose, the β-cell’s main stimulus, is taken up across the plasma membrane by the facilitative glucose transporter GLUT-2
Phosphorylation (P) of specific sites in PR couples multiple receptor functions, including transcriptional synergy in the presence of steroid hormones and growth factors predicted to activate MAPK and/or CDK2, and nuclear import or export (shuttling) in response to MAPK activation
A simplified schematic of T-cell development is shown with the main stages of development within the thymus labeled, key checkpoints and choice points indicated in red labels, and selected transcription factors indicated at major points when they must act
Alzheimer’s disease (highlighted in red) In Alzheimer’s disease, SIRT1 has been shown to promote non-amyloidogenic APP processing pathway by decreasing levels of ROCK1 kinase ()
A visual description of the signaling cascade is shown for the signal-receiving cell (i.e.
The TGFβ, PI3K, NFŒ∫B, and WNT pathways are some of the most important pathways interacting with NOTCH
Normal activation of MAPK pathway and pathway response to RAF inhibition
Signaling pathways mediating DON-induced RSR, including the MAPK (A, blue), NFŒ∫B (B, red), AKT and AMPK pathways (C, green)
DIANA-mirPath was used to predict the most likely molecular pathways targeted by PCR-validated DE-miRNAs in sarcoidosis lung tissue and identified the TGFβ pathway as the most likely candidate
DIANA-mirPath was used to predict the most likely molecular pathways targeted by PCR-validated DE-miRNAs in sarcoidosis PBMCs and identified the TGFβ/WNT pathway as the most likely candidate
Transcription factors that promote SSC maintenance are shown in green boxes
Testosterone signaling pathways in Sertoli cells
MUC1 regulates glycolytic flux by activating multiple signaling pathways, such as PI3K/Akt/mTOR, p53, and HIF-1α that regulate transcription of glycolytic genes
MUC1 modulates the overall metabolic flux to decrease the cellular levels of 2-ketoglutarate (2-KG), while increasing succinate levels
Signaling downstream of MUC1 regulates the expression levels of ROS-attenuating enzymes (SOD1/2, CAT, and GPx) and increases the flux through the pentose phosphate pathway (PPP) in order to fine tune ROS levels in cancer cells
The steps regulated by miRNAs are indicated by red bars
(Panel 5A) Expression levels of elements of the TGF-β signaling pathway following infection with wt-FV3
Angiogenesis Inhibitors (VSP Inhibitors) being tested in human cancer trials
Bioinformatic network analysis of the tazarotene-treated 10 h DE genes suggested that a significant number of the DE genes connected to the PI3K/AKT pathway as a central downstream node
Cellular functions of proteins commonly mutated in uveal melanoma
The data suggest that ALK1 signaling, triggered upon BMP9 binding, activates SMAD1,5,8 signaling, which induces expression of HES1, HEY1, and HEY2 together with Notch signaling
Pathways for sulfide biogenesis and clearance
The iron-regulated pathway and the inflammatory pathway are the two well-studied regulators of hepcidin
This is the general pathway discussed in the text
TGF-β1 receptor activation initiates both SMAD2/3 phosphorylation, via the ALK5/type I TGF-β1 receptor, as well as non-SMAD (e.g.
Brief Overview of DNA Damage Repair: Three common types of DNA damage are depicted in this image as well as an summary of the pathways/proteins that are activated in response to each type of damage
(A) Typical domain structure of the vertebrate Notch receptor and ligand... (B) Key steps involved in the activation of the Notch signaling pathway....
Ingenuity Pathway Analyses: Details are as in
Functional expression of JAK2 can be blocked at several levels
Role of the CD40–CD40L pathway during the CD8 primary response
The CD40-CD40L pathway plays a critical role in CD4 T-cell–mediated IL-21 production during the rescue of exhausted T-cell response
Arachidonic acid is metabolized by distinct enzymatic systems initiated by cyclooxygenase (COX 1 and 2), lipoxygenases (5-LOX and 15-LOX), and cytochrome (CYP) P450s
The three major modalities of DSB repair (NHEJ, HDR and MMEJ/SSA) are depicted
Schematic of the Wnt/β-catenin signaling pathway that responds to Norrin interaction with Frizzled4
Therapeutics in development that target survival pathways activated by LMP1 and LMP2a
D-PDMP inhibits ox-LDL induced LCS activity and atherosclerosis development
A. Regulation of vascular permeability by S1P/S1P1 signaling involves ligation of S1P to the S1P1 receptor to stimulate Rac1 activation via the Gi-dependent recruitment of PI3 kinase and Tiam1 to a common site.
Model for HRG-mediated signaling via mTORC2 to mTORC1
Core phosphatases of the PI 3-Kinase pathway
Induction of EMT and breast cancer progression through aberrant activation of Aurora-A kinase activity
Restructuring of adhesion at the apical ES and the BTB in the seminiferous epithelium during the epithelial cycle to facilitate the transit of developing germ cell across the epithelium is regulated by the intricate actions of polarity proteins (e.g., PAR6, 14-3-3, Cdc42) and actin regulatory proteins (e.g., Eps8, Arp2/3 complex, drebrin E) as depicted in this hypothetical model.
Signaling pathways that positively regulate ecdysteroidogenesis in the PG in Drosophila melanogaster
Schematic representation of a GC centrocyte, expressing a functional surface BCR, CD40 receptor and TLR/IL-1R
(A) In canonical Wnt/β-catenin pathway, binding of Wnts (‘Wnt on’) to a... (B) In noncanonical Wnt/Ca2+pathway, the binding of Wnts promotes Fzd-me...
Signalling pathways activated by chemokine receptors
Phosphoglycerate mutase 1 (PGAM1) controls the levels of allosteric regulators 3-phosphoglycerate and 2-phosphoglycerate
Scheme of participation of MC1R in regulation of melanogenesis
Scheme of the impact of MC1R on development of melanoma
Origins and removal of ribonucleotides in DNA
IL-15 impacts distinct cell types to mediate its pathogenic effects
(A) In WT embryos, mature muscles associate with their corresponding ten... (B) In msk mutants, the ECM matrix (blue) is reduced in size and the mus...
Current understanding of molecular mechanisms regulating spermatogonial stem cell (SSC) self-renewal in mice
Important mechanotransduction signaling pathways in striated muscle cells
A simplified diagram of the TLR-mediated and interferon (IFN)-mediated immunity in response to viruses
Major signal transduction pathways in GPCR agonist-induced hypertrophy and fibrosis.GPCR: G protein-coupled receptor.MP: metalloproteinase.PI3K: phosphatidylinositol 3-kinase.DAG: 1,2-diacylglycerol.GRB-2: growth factor receptor-bound protein 2.Sos: son of sevenless.PIP2: phosphatidylinositol (4,5)-bisphosphate.PIP3: phosphatidylinositol (3,4,5)-bisphosphate.PDK-1: phosphoinositide-dependent protein kinase 1.TSC-2: Tuberous sclerosis protein 2.GSK-3β: glycogen synthase kinase-3β.mTOR: mammalian target of rapamycin.eIF4E: eukaryotic translation initiation factor 4E.eIF2B: eukaryotic translation initiation factor 2B.eEF-2: eukaryotic translation elongation factor 2.eEF2K: eEF2 kinase.4EBP-1: eIF4E binding protein-1.S6K: ribosomal protein S6 kinase.ERK: extracellular signal-regulated kinases.MEK: mitogen-activated protein kinase kinase.ROS: reactive oxygen species.AC: adenylyl cyclase.PKA: cAMP-dependent protein kinase.PLC-β: phopholipase C isoform β.IP3: inositol 1,4,5-triphosphate.PKC: protein kinase C.PKD: protein kinase D.CaN: calcineurin.CREB: cAMP response element binding protein.HDAC: histone deacetylase.AP-1: activator protein 1.NFAT: nuclear factor of activated T-cell.Red arrows: adenylyl cyclase-PKA pathway.Purple arrows: PLC-pathway.Green arrows: Ca2+pathway.Light blue arrows: PKC pathway.Blue arrows: Raf-MEK-ERK pathway.Pink arrows: PI3K-Akt pathway.Orange arrows: ROS pathway.Purple arrows: Smad pathway
Pg co-activates TLR2 and C5aR in neutrophils and the resulting crosstalk leads to ubiquitination and proteasomal degradation of MyD88, thereby inhibiting a host-protective antimicrobial response
Inactivation of VHL in RCC cells triggers a cascade of signaling and HIFŒ±-dependent transcription that promote tumor growth cell autonomously, and by influencing angiogenesis in adjacent endothelial cells
S1PR2, sphingosine 1-phosphate receptor 2; Src, Src Kinase; EGFR, epidermal growth factor receptor; PPARŒ±, peroxisome proliferator-activated receptor alpha; NTCP, Na+/taurocholate cotransporting polypeptide; BSEP, bile salt export pump; PC, phosphotidylcholine; PECK, phosphoenolpyruvate carboxykinase; G6Pase, glucose-6-phosphatase; PDK1, phosphoinositide-dependent protein kinase 1; AKT, protein kinase B; SREBP, sterol regulatory element-binding protein; PKCŒ∂, protein kinase C zeta; FXR, farnesoid x receptor; SHP, small heterodimeric partner; MDR3, phospholipid transporter (ABCB4); GSK3β, glycogen synthase kinase 3 beta
Proposed model for the formation of reactive oxygen species at mitochondria, activation of Nrf2, and regulation of phase 2 gene expression in the nucleus
Comparison of apoptotic pathways and NLRP3 inflammasome activation
A. Under low amino acid conditions Ragulator is found in an inhibitory state with the v-ATPase and GATOR1 exerts its GAP activity towards RagA, keeping this GTPase in the inactive GDP-bound state that is not sufficient to recruit mTORC1.
Regulation of receptor-mediated endocytosis by CRL pathways
In renal fibroblasts, through binding to IGF-IR and via the activation of the PI3K and Akt/PKB pathways and mTOR, decorin induces the translation of fibrillin-1, a regulator of TGF-β availability
The VEGFR-2 homodimer (blue) and its phosphorylated residues known to facilitate signaling are shown
Insulin/mTOR signaling pathway and also the extrinsic modifiers that are present in diabetes
AngII directly induces multiple ECM protein synthesis including fibulin-2 and TGF-β
Stimulation of both, microvascular and macrovascular EC, with LTA/PepG triggers Rho, p38 MAPK and NFŒ∫B signaling leading to cytoskeletal remodeling, stress fiber formation and endothelial barrier dysfunction
Examples of pathway engineering and combinatorial biosynthesis to generate new analogs: A
Overview of the general innate immune response to viral infection
(a) EGFRvIII-mTORC2 axis promotes the activation of two independent down... (b) The chief metabolic pathways that contribute to the production of ma...
Interaction of kisspeptin, estrogen and BMP-4 in regulation of GnRH production by GT1-7 cells
Tumor cells become and stay dormant via signaling from the surrounding tissue (niche)
a. During a cognate interaction between APC and T cell, signaling through B7 costimulatory moleules and CD28 triggers local complement component production and release by both cells (~1000 fold more is produced by the APC) along with a transient downregulation of cell surface DAF and upregulation of C3aR/C5aR.
PHLPP (center) directly dephosphorylates and inactivates AKT, PKC, and S6K, at their hydrophobic phosphorylation motif (green circle) thus opposing cell survival and growth signals, and directly dephosphorylates and activates Mst1 at an inhibitory site (red circle), thus promoting pro-apoptotic signals
HMG-CoA reductase is a rate-limiting enzyme in the mevalonate pathway
Electrical activity of neurons results in the release of large amounts of K+ by these cells into extracellular space
atRAL is a major byproduct of the retinoid cycle with cellular toxicity
Numerous polymorphisms in genes encoding regulators of nucleic acid degradation or mediators of pathways involved in induction of or response to IFN-I, along with environmental factors that lead to cellular stress or oxidative damage, generate a host endowed with enhanced capacity to activate the IFN-I pathway
(A) In the absence of Wnt protein, newly synthesized β-catenin (Armadill... (B) In the presence of Wnt (Wingless is the homologue for Wnt-1 in Droso...
Sgk1 is induced by IL-23R signaling and is a substrate of PDK1 kinase a member of the IL-23R signaling pathway, which also includes Akt a kinase homologous to SGK1
Cellular mechanisms regulating steady-state and (chronic) stress erythropoiesis
Diagram showing the effects of knockout or blockade of specific elements of the alternative, classical and lectin pathways of complement activation on the pathogenesis of anti-MPO induced murine crescentic glomerulonephritis
The locus coeruleus (LC) projection to the hippocampus is essential for exercise-induced brain-derived neurotrophic factor (BDNF) expression
On engagement, the interferon-α receptor (IFNAR, which is composed of the IFNAR1 and IFNAR2 subunits) activates Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2)
Various receptor pathways cross-regulate the type I interferon (IFN) response; this alters the expression levels and activation states of IFN signalling components
Contextualizing Sharpin within the NF-Œ∫B pathway by comparative analysis of mutant transcriptomes
The Irinotecan Pathway, view of a model human liver cell showing blood, bile, and intestinal compartments, indicating tissue-specific involvement of genes in the irinotecan pathway
The BMP-7 protein is a secreted cytokine that normally functions to stimulate gene transcription by binding to its receptor and activating the Smad1/5/8 transcription factors
Schematic models of signalling pathways used by SDF-1/CXCR4 and GLP-1/GLP-1R in the activation of beta catenin/TCF7L2-mediated transcriptional expression of genes involved in beta cell survival and proliferation a SDF-1 activation of WNT signalling
Three commonly differentially expression MicroRNAs in pancreatic cancer tissue and patient blood: MicroRNAs 21, 155, and 200
Predicted network linking pancreatic cancer miRNA markers, known pancreatic cancer genetic lesions, and DAMPs
APC, antigen-presenting cells; mDC and pDC, myeloid and plasmacytoid dendritic cells; Hh, Hedgehog pathway; OPN, osteopontin; HSC, hepatic stellate cells
Phosphorylation of Foxo1 at S253 by Akt promotes Foxo1 cytoplasmic retention and ubiquitination, which serves as a central mechanism controlling Foxo1 stability and activity ()
A schematic cross-section of a podocyte foot process with the corresponding cell body, the glomerular basement membrane, and the glomerular endothelium is shown
Epidermal growth factor receptor (EGFR) pathway activation during HNSCC carcinogenic process
A model for the pathogenesis of T2D: adipose tissue, the pancreas, NLRP3 and T2D
The intrinsic pathway to apoptosis is initiated by activation of BH3-only protein
A, The cartoon represents the PI3K/AKT pathway
Cell membrane complexes located at tight junctions (Par3/Par6/aPKC), adherens junctions (cadherins/catenins) and the apical (Crumbs, Pals1, Patj) and basolateral (Scribble/Dlg1/Lgl) polarity complexes each signal to the core kinase cassette through poorly understood mechanism
Although many classes of GPCRs appear capable of promoting YAP activation, those like PAR1 that signal strongly through the GŒ±12/13 family are especially potent
The pathogenesis of ABC DLBCL involves constitutive activation of BCR, MyD88 and IL-6/IL-10 signaling pathway, promoting cell survival through NF-Œ∫B, STAT3 and PI3K signaling pathways
The role of GRK2 in cardiac insulin receptor signaling and myocyte glucose uptake
Hypoxic conditions and myeloid ecotropic viral integration site 1 (MEIS1) activate hypoxia-inducible factor 1α (HIF1α), which promotes glycolysis and HIF1α-dependent pyruvate dehydrogenase kinase (PDK) activation
PI3K–AKT signalling promotes the production of reactive oxygen species (ROS) by repressing the forkhead box O (FOXO)-mediated stress response
Increased levels of reactive oxygen species (ROS) activate the p38 MAPK–p16 pathway, which results in defective self-renewal activity and increased stem cell senescence
TLR and BCR signaling and integration in CSR and antibody responses
The many functions of promyelocytic leukemia nuclear bodies and PML as a negative regulator of the PI3-kinase/Akt/mTOR pathway
Autophagy in mammalian cells can be activated by various stimuli
Receptor tyrosine kinases (RTKs), activated by growth factors (GFs) signal through several pathways to drive changes in the transcription of specific RNAs
Model of combinatorial cytokine regulation of iNOS expression in IMF
Working model of apigenin-induced DNA damage
(a) Schematic of major steps in the insulation... (b) Phosphotransfer specificity of EnvZ, RstB,... (c) Schematic summarizing the distribution of h...
Intracellular glutamate is converted to glutamine in astrocytes and is exported to the extracellular space
Activation of the EGFR-Ras-MAPK pathway in C. elegans vulval development is initiated when LIN-3/EGF ligand secreted by the gonadal anchor cell (AC) binds to the LET-23/EGFR receptor, causing it to dimerize and undergo autophosphorylation (; ).
TNFŒ± causes the activation of ERK, JNK, and p38 MAP kinases
MAPK regulates TNFŒ± expression by several mechanisms
A. Strong activation of the TLR4-MD2 receptor complex is achieved when smooth and rough LPS first bind to LBP and CD14 to then trigger TLR4-MD2 activation.
The enzymes catalysing the individual reactions in M. tuberculosis H37Rv and M. smegmatis mc2155 are shown in the scheme.
Proposed frame work for mRNA nanoparticle mediated tumour vaccination
Role of PTEN in PI3K/AKT/mTOR signaling and cell proliferation following growth factor binding to its receptor
Caveolae are receptor-rich regions of the plasma membrane, populated by multiple receptor types including BMPR2 and TGFβ receptors
(A) A simplified model for a partially conserved nutrient signaling PKA pathway in yeast and mammalian cells
Salinomycin exerts its inhibition on Wnt signaling pathway through its suppression on the phosphorylation of LRP6 and the expression of β-catenin and p-GSK-3β
Growth factor signaling (not shown) and cell adhesion are required for transmitting signals to the Ras/Mek/Erk signaling pathway, which then stimulates cell proliferation via increasing cyclin D1 transcription and degrading the cyclin dependent kinase inhibitors p21 and p27
The central pacemaker controlled autonomic nervous and neuroendocrine systems (ANS and NES) rhythmically signal to all of their target tissues
KSHV encodes viral interferon regulatory factors (vIRF 1-3) that antagonize the function of cellular IRFs, p300, and NFŒ∫B to suppress production of type I IFN
Second messenger signals at the leading edge of polarized ameboid cells ()
(A) Severe ER stress induces pro-apoptotic signaling from the ER (IRE1 and PERK) that leads to mitochondrial Ca2+ overload
(a–b) During EGFR TKI treatment, a β3-positive cancer stem cell population is selected
Model of arteriovenous EC specification during embryonic development
(A) In pluripotent conditions or in the absence of RA, the canonical Wnt signaling pathway activation culminates with Tcf1 and β-catenin binding to selective Wnt response elements (WREs; white boxes) and induction of the transcription of genes necessary for pluripotency/stemness
The mammalian target of rapamycin (mTOR) complex, particularly mTORC1, integrates multiple signals derived from growth factors, hormones and energy status
The mTOR pathway can become hyperactive (thick lines) by mutations of genes encoding upstream regulators (TSC1, TSC2, STRADA, PTEN or NF-1), components of the pathways that converge on TCS1/2, such as RAF, AKT, PI3K and also of mTOR (highlighted in red)
Notably, activation of the TLR/MYD88 pathway may directly contribute to pro-survival signalling via NFŒ∫B as well as via enhanced secretion of IL10, which probably promotes pro-survival signals via the JAK/STAT pathway
When an infected sand fly releases Leishmania promastigotes into the skin, they evade immediate host immune response and destruction by seeking refuge in different types of host cell, which includes dermal macrophages (), fibroblasts, keratinocytes and dendritic cells (DCs)
Chalcones with minor structural changes result in distinct processes of cell death
Involvement of uPAR-β3 integrin signaling in calcineurin/NFAT activation-induced podocyte injury and proteinuria
(a) Multiplex immunoprecipitation detected by flow cytometry (MIF) is us... (b) Stimulation of human peripheral blood T cells by plate-bound anti-CD...
Differential LSEC Signalling in Models of Acute or Chronic Injury
SP600125 and BCI Inhibition in MAPK Signaling Pathway adapted from KEGG 04010
LDN Inhibition in TGFB Signaling Pathway adapted from KEGG 04350
The SMN complex—depicted with known integral subunits according to []—and the protein and RNA components of each of its proposed RNP targets are shown above the RNA pathway in which they function
Rigosertib is a multi-kinase inhibitor that can influence signaling of multiple pathways important for cellular proliferation and survival
(A) Merlin activates the Hippo pathway to suppress YAP/TAZ through regulation of core kinase components at the plasma membrane, through inhibition of the CRL4DCAF1 E3 ubiquitin ligase in the nucleus, and by regulating cell junction-associated proteins that modulate Hippo signaling
Cross-antagonistic and self-re-enforcing metabolic signaling in HSCs.Upon activation by receptor tyrosine kinases (RTKs), the PI3K-mTOR axis drive HSC proliferation and differentiation by increasing ROS production and repressing the FAO signaling module
(A) Known IPA (Ingenuity Pathway Analysis) DNA repair network of gene/protein (nodes) interactions (edges)
Tbx18 is specifically expressed in cells of the SAN “head” region and is required for its morphogenesis in part by repressing Cx43, although the downstream effectors of this pathway remain largely uncharacterized
Mutations in MMR genes either inhibit (red) or impair (yellow) common steps in Exo1-independent or Exo1-dependent MMR as well as steps that are specific to Exo1-independent MMR
Intracellular signaling pathway implicated in the regulation of ENaC activity by bradykinin in the distal nephron
A. Chemokines likely regulate immune cell trafficking in the inflammatory bowel diseases.
Ubiquitination of RIP1 is an early pro-survival checkpoint in TNF signaling
(a) The cell cycle controls the competition between NHEJ and HR in DSB r... (b) The DDR results in HR activation and inhibition of cell cycle progre...
The dual functions of guggulsterone in the regulation of BSEP and possible mechanism for its cholesterol-lowering effect
Paks control critical cellular events required for angiogenesis, including endothelial cell proliferation, survival, attachment and migration
Caspase activation by extrinsic apoptosis requires binding of the trimeric TNF family of death receptors by their cognate ligands such as TRAIL and FasL
The cartoon depicts IL-15 mediated activation of the PI3K/ERK1/2 and JAK1/STAT3 pathways
The Ras/MAPK signal transduction pathway
Canonical Mitogen Activated Protein Kinase (MAPK) pathway signaling
The ligand, its receptor, and core signal transducers are indicated
Through LET-23/EGFR receptor, the graded inductive signal, LIN-3/EGF, secreted from the anchor cell (AC) promotes the 1° fate and activates expression of genes encoding ligands for the LIN-12 receptor in P6.p.
Model depicting the postulated mechanism for increased QHREDGS-dependent hPSC survival, wherein the binding of QHREDGS to a β1-integrin receptor on the hPSC surface increases ILK, stimulating the upregulation of the pro-survival ERK1/2 signaling pathway and the eventual downregulation of caspase-dependent apoptotic pathways
The rate of formation of nascent adhesions depends on the ECM concentration, and the rates of nascent adhesion formation and turnover depend on the velocity of membrane protrusion
Major physiological functions of the endoplasmic reticulum and their perturbations cause ER stress and activate the unfolded protein response
Role of Foxo proteins in cardiac hypertrophy
Molecular Mechanisms of Neurodegeneration in PD
Possible pathway for a role of H1N1 seasonal infection and Pandemrix vaccination in onset of narcolepsy: the seasonal H1N1 influenza infection or the Pandemrix vaccine could stimulate auto-reactive T-cells or B-cells targeting towards hypocretin producing neurons via several different mechanisms
Simplified schematic diagram of the IL-8 signaling pathway in neutrophil chemotaxis
A) 1205Lu cells were treated with 1 ŒºM vemurafenib overnight
Vemurafenib treatment relieves a negative feedback on ERBB3 transcription resulting in an increase of ERBB3 at the membrane
Activation of G protein coupled receptors (GPCR) and receptor tyrosine kinases (RTK) initiates activation of parallel signaling cascades that culminate in actin filament remodeling, changes matrix adhesiveness and regulation of myosin II motors that generate traction force
In response to intrinsic death stimuli originating from the nucleus (chemotherapeutic drugs) or mitochondria (ROS) influence the release of cytochrome c controlled by the proapoptotic Bcl-2 family
Multiple growth factor receptors are activated at the cell surface during cancer
Lef-1/ TCF proteins are the downstream DNA binding effectors of canonical Wnt signaling pathway
Oncogenic drivers in ALCL cells dirout intrinsic pathways leading to a self autonomous cell growth and overcoming host confinements; ALCL cells are also capable to modulate immunoresponsiveness changing the function of regulatory and effector T-cell through alternative mechanisms including antigen-camouflaging and producing lymphokines able to suppress immune-sorveillance (i.e.
Most FcγRs have a common Œ± chain that contains an extracellular region with varying numbers of the immunoglobulin (Ig)-like domain
On the left, fibronectin promotes ET-1 production by activating Src, which, in turn, activates a Shc/Grb2/Sos complex by direct phosphorylation of Shc; phosphorylated Shc then activates the ERK signaling pathway, which leads to increased preproendothelin-1 expression
Aβ oligomers activate several ‘stress-response’ kinase pathways in neurons
Crosstalk of BMP and neurotrophin signaling in neurons
Schematic of BMP signaling in promoting axon regeneration
A representative diagram of a renal proximal tubule epithelial cell and the drugs that are involved in preventing the reabsorption of uric acid into the body
IL-17 and IL-22 bind to transmembrane heterodimeric cell surface receptors to induce cellular signaling pathways
In macrophages, P. gingivalis interacts with CD14 and the TLR2/TLR1 signaling complex resulting in inside-out signaling for activating and binding CR3, which leads to a relatively ‘safe’ uptake of these organisms by macrophages (; ; ).
Lymphatic endothelial cell (LEC) markers shown to be variably expressed in Gorham tissues include cluster of differentiation (CD)-31 protein, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, and CD105
The expression of HRI increases during erythroid differentiation from BFU-E to reticulocytes
current targets of nuclear DNA repair pathway proteins and their functions
Ingenuity pathway analysis (IPA) revealed TGF-beta signaling as the top “connected” network of differentially methylated candidates in HDM-exposed group
CpG or viral mediated activation of TLR9 leads to recruitment of MyD88 and TRAF6, and subsequent phosphorylation of IRF7, which promotes its translocation to the nucleus resulting in transcriptional activation of type I IFN genes
Model of mechanisms of androgen neurotoxicity and neuroprotection
The expression of KLF4 is inhibited by DNA methylation, microRNA and ubiquitin-proteasome pathway
EMT is a product of crosstalk between signaling pathways, including TGF-β, Wnt/β-catenin, Notch, FGF, STAT3 and EGF
Wnts organize presynaptic (CNS and NMJ) and postsynaptic (NMJ) specializations through multiple signaling pathways
Schematic models for the assembly of cohesin and associated factors at double-strand breaks (DSBs), and ATR- and Eco1 (Ctf7)-dependent reactivation of cohesin in G2 phase
Diagram depicting hypothetical mechanisms by which the polycystins directly affect gene transcription and regulate the cell cycle
Models of Ras signaling in NF1-deficient GBM cell lines
(a) Canonical non-Smad pathway tumor growth factor (TGF)-β signaling. (b) Transcriptional regulatory module controlling the mesenchymal signat...
Pre-pro ET-1, the canonical precursor is synthesized as a product of transcription from preproendothelin , a 203-amino acid peptide that cleaved at dibasic sites by furin-like endopeptidases to form intermediate ETs, and then big ET's which are 38 to 40 amino acid residues
Schematic of insulin signal transduction through canonical IRS1/PI3K pathway and through abbreviations: Cbl/CAP/TC10 pathway associated with lipid rafts in the plasma membrane
Protomural role of tumor-associated macrophages (TAM)
Mutations observed in the PI3KCA and p85Œ±
A model for Hh signaling in the absence (left) or presence (right) of Shh
Left, Gpr161 localizes to primary cilia in a Tulp3/IFT-A-dependent manner []
To understand the metabolic pathways disrupted in HCC at the genetic, mRNA, and metabolite levels, we used data from the Liver-SB/HBV screen (), human expression data, and metabolomic results ()
In DNA damage-dependent pathway, Chk2 is activated by ATM kinase in response to ionizing radiation
a, The proposed model of protective (blue) and pathogenic (red) effects of lipid antigen presentation in intestinal inflammation
DKK1 protein is a classical inhibitor of Wnt signaling pathway that typically antagonizes Wnt/beta-catenin signaling, by binding to the Wnt co-receptors Lrp and blocking their interaction with Wnt and transmembrane co-receptors Frizzled
Coxiella burnetii binds to macrophages through Œ±Vβ3 integrin, which triggers phagocytosis of the bacterium through an actin-dependent mechanism
A new family of type IV secretion system (T4SS) effectors has been identified that localizes to the Coxiella-containing vacuole (CCV) and might have diverse functions, such as CCV stability and fusogenicity
Therapeutic strategies to target mutant NRAS: Direct targeting strategies include inhibition of RAS transcription by RNA interference and blockade of posttranslational modification by farnesyltransferase inhibitors
Mutant proteins are indicated with asterisks and are circled
(A) Foreign antigens such as dsRNA and lipopolysaccharide bind to Toll-l... (B) Acanthoic acid derivatives had shown to have anti-inflammatory activ...
Following antigen binding to BCR, the co-receptors IgŒ± and Igβ signals to activate downstream molecules phospholipase Cγ2 (PLCγ2) and the phosphoinositide 3-kinase (PI3K) pathway
After ligation of BCRs, Src kinases phosphorylate ITAMs, where SYK binds and is also activated by phosphorylation
Pro-B cells (Fraction B) proliferate under the influence of the IL7 receptor (activation of JAK-STAT5, AKT) until they rearrange Ig VH-DJH gene segments to express a functional μ heavy chain (μ HC) as part of the pre-BCR (Fraction C’)
Cellular and molecular interactions between HCL cells and their microenvironment
Genes with mutations known to associate with PAH are shown in red, with possible resultant effects of the actions briefly listed
Overview of the major signaling pathways involved in regulation of renin
Model of GŒ±i-mediated activation of the PI3K-Akt-mTORC1 pathway in response to EGF
In the presence of sclerostin-neutralizing monoclonal antibodies (Scl-Ab), the osteocyte-produced Wnt signaling pathway antagonist sclerostin is prevented from binding to the Wnt co-receptor LRP5/6
A network was generated around the Aurora-A (AURKA) and Aurora-B (AURKB) proteins was generated by the cBio portal [] using data from Pathway Commons regarding protein-protein (HPRD), enzymatic (Reactome ) and pathway (NCI-Nature Pathway Interaction Database) interactions
A schematic representation of cPAcP interaction with HER-2 and PI3K/Akt pathway in regulating prostate cell homeostasis
The binding of insulin to its receptor on cell membrane results in insulin receptor (IR) tyrosine kinase activation and IR tyrosine phosphorylation
The insulin/IGF-1-like pathway is conserved among various species and suppressing this pathway extends lifespan in species such as worm, fly, and mouse
Graphic representation of the Pten/PI3K/Akt signaling pathway
Positive feedback loop involving the oxLDL/LOX-1 signaling pathway and LOX-1 modulators
LOX-1 signaling mechanistically links atherosclerosis, hypertension, and diabetes
Genes in the pathway are circled as follows; Blue: up-regulated potential target proteins in mucinous subtypes; Red: up-regulated proteins in mucinous subtypes with less fold change; Yellow: proteins identified in glycoproteomics with no change in relative abundance based on spectral count.The following annotations were used; a Proteins observed more in M-LAC bound fraction; b Proteins observed more in unbound fraction; c Proteins observed equally in both unbound and bound fractions.
Intestinal SIRT1 is an important regulator of systemic bile acid homeostasis
(A) Under wild type conditions, increasing levels of BMP activity over d... (B) Gene regulatory network underlying digit chondrogenesis. Threshold l...
BCR engagement induces a cascade of phosphorylation/activation of the pathway kinases (e.g.
The sirtuin SIRT1 silences the miR-134 promotor either by deacetylating the histones, which allows for formation of higher-order chromatin structure (shown), or by targeting acetyl groups on other unknown proteins
TNFŒ± promotes ET-1 production by activating the IKK complex, which, in turn, activates ERK and JNK via their direct phosphorylation; phosphorylated JNK translocates to the nucleus to activate c-Jun, which binds to the preproET-1 promoter and triggers preproET-1 mRNA and protein expression
The Ras/MAPK signaling cascade and small molecule inhibition
After binding to its receptor (1), speract stimulates a membrane guanylyl cyclase (GC), which elevates cGMP (2) that activates tetrameric cGMP-regulated K+ channels (tetraKCNG), causing a membrane potential (Em) hyperpolarization (4) due to K+ efflux (3)
Schematic of myocardial abnormalties revealed in human HFpEF
Schematic summary indicating the mechanism by which Cdt, specifically CdtB, affects the PI-3K signaling pathway and the production of pro-inflammatory cytokines
Model of MIF-CD74-Lyn signaling cascade during osteoclastogenesis
Endosomal TLR7 in pDCs can bind single-stranded RNA (including, but not limited to viral genomes), and trigger a MyD88 dependent kinase cascade that leads to the activation of IRF7
Model for GATA regulation of Notch signaling in the intestine
(A) In the absence of BMP binding (top panel),... (B) BMP typically binds to the type II receptor... (C) The recently discovered type III receptors...
Opposing functions for small RNA pathway activity during the antiviral response
Gaps in conventional treatment of heart failure include deranged β-AR signaling, distorted Ca2+ cycling with depletion of SR Ca2+ levels, diastolic dysfunction, and cell death
(A) miR-UL112-1 targets viral fact... (B) miR-US25-1 targets cellular ge... (C) HCMV miRNAs target genes invol... (D) HCMV miRNAs target the secreto...
Interferon (IFN)-inducible proteins are required for host resistance to intracellular bacteria, a Specific immunity-related GTPases (IRGs).guanylate-binding proteins (GBPs) and other GTPases translocate to compartmentalized bacteria in phagosomes or inclusion bodies.
Transcription of the MC1R gene leads preferentially to the MC1R-001 transcript (1)
Binding of SHP2 on ITSM and a yet unidentified partner on ITM of PD-1 inhibits TCR-mediated activation of the PI3K/Akt pathway and the PLCg-1/Ras/MEK/Erk1/2 pathway
IL-1Œ± and IL-1β synthesis and signal transduction pathway
We hypothesize that WWOX is a key component contributing to the regulation and homeostasis of the TGFβ pathway likely in two critical ways: Firstly by binding and preventing the nuclear translocation of receptor-regulated SMADS (R-SMADs) that all contain PPxY motifs (PY box) such as SMAD3 (regardless of their phosphorylation status) and of key co-activators such as RUNX2, thus preventing the transcriptional activation of pro-metastatic genes
There are two apoptosis pathways, intrinsic and extrinsic
Coactivator dependent signaling regulates various biological functions, and deregulation causes diseases
(A) B7 family members: CTLA-4, ICOS, ICOSL, PD-1, PD-L-1 and PD-L2. CTLA... (B) Signalling pathways influenced by CD69 and Gal-1. CD69 is early indu...
(A) SOCS proteins interfere with Jak-STAT pathways induced by the interl... (B) IDO is expressed mainly on DCs and macrophages. Its expression is re...
The bimodal pathway of Notch signaling during pancreas development
Inferred connectivity maps for differentially expressed genes in (A) the “inflammatory response” network and (B.)
Model for the integration of the p38 MAPK signaling pathway with Mef2-dependent recruitment of the Ash2L complex to muscle-specific promoters
Proposed model of SE-induced progenitor proliferation: Pilocarpine-induced SE triggers glutamate release, resulting in excitotoxicity, inflammation and reactive microgliosis in the SGZ
Binding of TNF-Œ± to its receptor causes the recruitment of TRADD, FADD, and TRAF-2 proteins and activates TAK1
A, The PI3K/AKT/mTOR pathway is tightly regulated by multiple feedback loops (dashed lines) to control growth factor signaling
Growth factor- and cytokine-regulated pathways are activated during liver regeneration
Regulation of glutamine and glucose metabolism defines the ability of hematopoietic stem cells (HSC) to differentiate into erythroid versus myeloid lineages in vitro and in vivo
Combined inhibition of PI3K and Akt (indicated by the dashed bracket) is synergistic only in resistant models that maintain PIP3 and phosphorylation of Akt substrates (453R, T47DR)
Saturated fatty acids (SFAs) stimulate inflammatory pathways through Tlr4 dependent and independent mechanisms
MiR-696 is downregulated with exercise and motor nerve activity, which leads to an increase in peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1), a potent transcriptional coactivator that regulates genes involved in energy metabolism
(A) Functional involvement of USP1... (B) Therapeutic silencing of miR-1... (C) Antimetastatic therapeutic str... (D) DUBs or their downstream signa...
Inhibition of protein synthesis by rocaglamides
Apoptosis pathways affected by rocaglamides
The establishment of PCP across the organ of Corti requires a three-tiered regulation: (1) upstream factors for directional information along the mediolateral axis of the cochlea; (2) core PCP proteins form polarized complexes along the mediolateral axis of the cochlea; (3) unknown cellular mediators link polarized core PCP complexes to the machinery that builds the “V”-shaped stereocilia in individual hair cells and orient the vertices of the “V”-shaped stereocilia toward the periphery of the spiraling cochlea, establishing uniformly oriented stereocilia across the organ of Corti
The development of the auditory sense organ
Mechanism of converting epigenetic marks
Multiple targets of lung cancer related key miRNAs are evidenced, as well as the variety of downstream effects
The molecular pathogenesis of thyroid cancer involves dysregulation of the mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase (PI3K)/AKT, and the TSHR cAMP signaling pathways
The major precursor PA is synthesized in the ER and mitochondrial outer membranes
Proposed molecular interaction between two neuropathologies such as major depressive disorder and Alzheimer’s disease
A model is presented whereby serine phosphorylation of IRS-1 serves as a mediator of Ang II to inhibit insulin-induced Akt Thr308 phosphorylation
ATX hydrolyzes lysophospholipids, in particular lysophosphatidylcholine (LPC), to produce bioactive LPA
A, The third most significant network (Fisher's Exact Test, p<10-42) constructed by IPA from genes with confirmed somatic mutations in BC, including KDM6A and RB1 (highlighted in blue)
An overview of the modulatory effects of low-dose H2O2 on the functions of pDCs
The IGF but not the EGF signaling pathway is regulated by the NEDD4-PTEN circuitry
Inactivating mutations in PTCH or binding of Hh ligands to PTCH de-represses SMO thereby allowing its translocation onto the tip of the primary cilium leading to transcriptional activation of Gli1/2
The Hh signaling pathway demonstrates complex crosstalk with multiple signaling pathways that modulate cancer pathogenesis
Schematics of the core pathway components and how they interact
Outline of a cell with nucleus and the Hippo pathway network
Cytokines are structurally diverse and bind to structurally distinct receptors
In response to S1P, the S1PR1 signaling pathway may increase endothelial barrier function by stimulating actin-dependent outward spreading of endothelial cells and suppressing cellular contractility
Genes/gene products are represented graphically as nodes and the biological relationship between two nodes is represented as an edge (line)
Schematic depicting pH- and serotonin-mediated inactivation of TASK channels
a. The p53 and RB pathways regulate G1 cell cycle checkpoints.
Proposed model of tetrandrine-induced apoptosis in prostate cancer
A. Upon upstream activation, RAS becomes activated, resulting in signal transduction through RAF, MEK and ERK.
A. PI3K can become active, under physiologic conditions, via upstream RTK signaling and/or RAS.
Tumstatin, endostatin, arresten and canstatin interact with αVβ3/ α3β1, α5β1, α1β1 and αVβ3/ αVβ5 integrins respectively, to inhibit the phosphorylation of focal adhesion kinase (FAK)
DENV RNA is recognized by pattern recognition receptors TLR-3 (A) and MDA5 and RIG-I (B), resulting in a signaling cascade that induces IFN-Œ±/β production
DENV manipulates host cellular processes and innate immune responses within infected cells by A) manip... B) To of... C) The D... D) Durin... E) The D...
A mechanistic model depicting the factor association of DDB2 and XPC with ATR and ATM, influencing the DDR pathway in response to UV damage
The seven FDA-approved agents for the treatment of kidney cancer targeting the von Hippel–Lindau (VHL) tumour suppressor pathway
STING, an endoplasmic reticulum transmembrane protein, forms homodimers and functions as an adaptor for cytosolic DNA sensing
A putative model for the formation of stable and labile LTM of aversive (fear) and appetitive (drug) stimulus
βOHB production is controlled by at least two nutrient-responsible pathways that are implicated in longevity and may be subject to regulation by βOHB via HDAC inhibition
ATM/ATR pathways regulate HR and NHEJ in response to oxidative DNA damage
Proposed model of gene expression up regulation of TLR signaling and CXCR4/7 in human liver MDB formation
Genes in the ribosome biogenesis pathway on the microarray in the context of the corresponding KEGG pathway representation are marked in green
Transcriptional factors including TCF/ LEF, CBF-1 and GLI following the activation of Wnt, Notch1 and Hh respectively, work cooperatively to organize the self-renewal and cell proliferation of CSCs; Wnt activation inhibits GSK3β causing the activation of β-catenin to control the Wnt pathway, which together with CBF-1 and GLI helps maintain the CSC phenotype
Final summarized parameter ranking according to  with respect to (a) tumor volume and (b) tumor expansion rate
Perpetuation of innate immune responses in sJIA
Secretion of IL-1β by monocytes in inflammatory diseases
Intracellular signaling mechanism triggered by CSPG present in the glial scar
(1) Anti-survival signaling mediated by GPCRs, such as the cannabinoid receptors, is dependent upon an increase in ceramide following the induction of serine palmitoyltransferase, which is the rate-limiting step in de novo ceramide production
Hypothesised mechanism by which the tetrapeptide N-acetyl-seryl-aspartyly-lysyl-proline (Ac-SDKP) inhibits fibrosisAc-SDKP is generated from the G actin binding peptide, thymosin β4, by prolyl oligopeptidase (POP) through one-step enzymatic cleavge
Cytokines or interferons bind their cognate receptors and initiate a signaling cascade leading to activation of the latent transcription factors STAT and ultimately gene transcription
Proposed TLR signaling mechanism by CS14K: a hypothetical model of TLR4 signaling, pathway activated by fusion protein, in a MyD88-independent fashion
Type I, II and III IFNs bind to their specific receptors on the cell membrane and trigger JAK-STAT signaling pathway
Nutrient-induced cell proliferation in the crypt
A putative pathway from cAMP to ERK in PACAP-mediated neurite outgrowth in PC12 cells
Diagram depicts a model in which Eya2 and Ebf3 are positioned in the gene regulatory pathway for the development of RGCs
Schematic diagram and proposed model for the metabolic regulation and coordination of the leptin mediated reproductive and nutritional axes
Representative image of an apoptosis pathway that was significantly enriched for in prostate cells treated with SFN for 24 hours
Innate sensing of zymosan via TLR2 efficiently induces Akt and Erk activation
(A) T cells are activated when their TcR and CD28 receive antigen-specif... (B) Crystal structure of the extracellular PD-L1:PD-1 complex (human PD-...
Ang II stimulates various signaling pathways including reactive oxygen species (ROS) that culminates in the activation of intracellular kinases (MAPK)
Tumors up-regulate detoxification enzymes like GSTs, which play a vital role in buffering the toxic effects of oxidative-stress by catalyzing the glutathione-conjugation of the products of lipid peroxidation like 4-HNE in the initial step of mercapturic acid pathway (MAP)
Specific signaling pathways maintain the resting platelet state (a) or initiate platelet activation (b)
CTLA-4 coligation can reverse AICD induced by ligation of the TCR complex
Schematic representation summarizing the intracellular events involved in the neurotrophic activities of PACAP on PC12 cells
A mitochondriocentric signal-transducer-effector pathway to nonischemic cardiomyocyte necrosis
Schematic representation of asTF signaling pathway
The signaling pathways illustrate validated targets of miRNAs and miRNA families that control smooth muscle-restricted gene expression by serum response factor (SRF) and its co-regulators myocardin (Myocd), KLF4, KLF5 and Elk-1
The schematic shows common upstream signaling mediators and the major signaling pathways transducing pro-inflammatory signals in smooth muscles Conserved kinase cascades (JAK/Stat, NFŒ∫β, ERK1/2, p38MAPK, and JNK1/2) have been described in all smooth muscles that regulate pro-inflammatory as well as miRNA gene expression
Schematic illustrating mechanisms of SR-A intracellular signaling
FPR on glioblastoma cells is activated by agonists released by necrotic tumor cells
Insulin regulates HGP by activating the IRS-PI3K pathway, which is coupled to the recruitment and activation of AKT, the key insulin signaling intermediary that inhibits the transcription factor FoxO1
Kidney cancer is not a single disease; it is made up of a number of different types of cancer with different histologies, having different clinical courses, responding differently to therapy and caused by different genes (e.g., VHL, MET, FLCN, FH, SDHB/C/D, TFE3, TFEB, MITF, TSC1, TSC2 and PTEN)., The PTEN gene, which is frequently found to be mutated in the germline of patients affected with Cowden Syndrome, encodes for a plasma membrane lipid phosphatase that inhibits the PI3K signaling pathway.
Schematic of fear circuitry subserving unconditioned and conditioned fear derived from animal data
The path highlighted in orange (a) is extracted and presented in a top-down layout (b)
However, when tested in clinical trials, TNF-alpha inhibiting compounds were not effective against GVHD but could later be repositioned for the treatment of Rheumatoid Arthritis (focus pathway)
The activation of death receptors (TNFR1, Fas, and TRAIL), TLR3, TLR4, or the TCR can result in apoptosis or necroptosis
Common mutations in glioblastoma are observed throughout cell cycle regulatory pathways
In the absence of an upstream ligand, receptor Frizzled (FZD) and co-receptor LRP5/6 are inactive (1)
A. Schematic of glycolytic pathway and its interaction with tricarboxylic acid (TCA) cycle and pentose phosphate pathway.
Schematic depiction of the role of OGG1-initiated DNA base excision repair in an innate immune response
Activation of the transcription factor CREB by the NMDA signal transduction pathway
Schematic diagrams of Wingless and Arm structure, and pathway relationships
(A) Anti-phosphotyrosine (pY) immu... (B) Venn diagram of the number of... (C) Ingenuity Pathway Analysis (IP... (D) Network analysis of the 23 pro...
Signaling molecules, including cytokines and pattern recognition molecules, are important for intestinal epithelial cells (IECs) responses during inflammation
Simplified outline of the MyD88-signaling pathway by which TLR agonists induce the production of inflammatory mediators
The B-cell receptor (BCR) and its downstream pathways
Multiple event model for B-cell lymphomagenesis
The HER family comprises four members, each of which is activated by one or more of the 13 identified members of the epidermal growth factor (EGF) family of ligands (shown above each receptor)
During homeostasis several endogenous mechanisms exist to modulate EGFR pathway activity
Three strategies are used to antagonise aberrant EGFR signalling
Intestinal BA uptake has direct and indirect impact on hepatic BA homeostasis
We propose a signaling pathway involving the crosstalk between epithelial Ihh signaling to Gli1 within the mesenchyme, then relaying to an intermediate mediator, such as Wnt, to induce proliferation
The tyrosine phosphatase SHP2 is required for the proper timing of neurogenesis and gliogenesis and the balance between them during CNS development
(Left) ERK1/2 pathway inhibition by vemurafenib leads to downregulation of DUSP and SPRY proteins
A variety of cell-intrinsic and -extrinsic stresses can activate the cellular senescence program
Panel A: WNT pathway. The extracellular ligand WNT... B: SHH pathway. In canonical Hedgehog signali... C: MYC pathway. Signaling through receptor ty...
Metabolism and bioactivation of carcinogenic aromatic and heterocyclic amines
Cartoons of protein C activation and APC signaling in the membrane lipid-rafts of endothelial cells
Cartoons of PAR1 activation by thrombin in the membrane lipid-rafts of endothelial cells when EPCR is free or occupied by its natural ligand
A) Network analysis of KEGG pathwa... B) Heat map of up-(red) and down-r... C) Schematic of the NLR pathway. R... D) NLR inflammasome genes differen...
Interactions between alcohol-induced mechanisms leading to hepatic carcinogenesis
Bile acids activate FXR, TGR5 and cell signaling pathways to inhibit CYP7A1 and CYP8B1 gene transcription
The Notch receptor is translated as a full-length protein but it is cleaved in the trans-Golgi network into two subunits by furin-like convertases
Binding of endothelins to their receptors initiates a series of intracellular signal transduction events via heterotrimetic G-proteins
Depicted are all proteins identified by drug affinity chromatography after background subtraction (as described for ) supplemented with all phosphoproteins identified by phosphoproteomics
Mechanisms of resistance to BRAF inhibitors
Predicted miR-340 targets are oval and outlined in a solid line and targets found to be predicted and regulated by miR-340 are oval and outlined in a dashed line
Schematic diagram of EGF signaling pathway to stimulate proliferation of conjunctival goblet cells
Schematic diagram of signaling pathways used to stimulate mucin secretion in conjunctival goblet cells
Signaling through PI3K/mTOR and Ras/Raf/MEK/ERK pathways is controlled by negative feedback loops
A) Compensatory over-activation of signal transduction pathways induced... B) Compensatory over-activation of signal transduction pathways induced...
YAP activity is regulated by phosphorylation, subcellular localization, and degradation
The mTOR complexes integrate signals from nutrients, growth factors, cytokines, and various intracellular influences to elicit a variety of crucial cellular responses
The small inset at the top depicts the physiological regulation of mTOR signaling by a variety of intrinsic and extrinsic factors
Nitric oxide (NO) by activating soluble guanylate cyclase (sGC)-cyclic guanosine-3′,5′-monophosphate (cGMP) signal transduction pathway mediates various physiological/beneficial effects including vasodilation, inhibition of platelet aggregation, anti-inflammatory, anti-remodeling and anti-apoptotic effects
Generalized schematic of MAP kinase signaling demonstrating the points of pathway activation for cancer models shown to overexpress Mmp1a
The isoprenoid biosynthetic pathway (IBP) and pharmacological inhibitors
VEGF-activated PKD1 phosphorylates class IIa HDACs (HDAC 5 and 7) and induces those cytoplasmic accumulations in endothelial cells
In resting cells, Csk binds to VE-cadherin through constitutive phosphotyrosine Tyr-685-dependent interaction
A. Extracellular growth factors bind with cell receptors, activating a series of intricately regulated signaling.
Pathways for initiation and maintenance of psoriasis
Committed metabolites (shaded circles) and functional roles (other shapes) are marked by abbreviations defined in the text and color coded to reflect the main pathways: de novo synthesis of NaMN from L-Asp (green); common pathway from NaMN to NAD(P) (red), pyridine salvage (blue), pyridine nucleoside salvage (magenta)
Each node represents the active “on state” of the protein
BN results are shown on the left, GBN results on the right
BN and GBN results from synthetic data, using one perturbation per sample
a | In order to escape dormancy and become proliferative dormant disseminated tumour cells (DTCs) can inhibit bone morphogenetic protein (BMP) signalling by expressing inhibitors such as COCO
Key signaling nodes in prostate cancer that regulate epithelial plasticity
TLR1, TLR2, TLR4, TLR5, and TLR6 are expressed at the cell surface for extracellular ligand recognition whereas TLR3, TLR7, and TLR9 are localized in the endosomal compartment for the recognition of pathogen nucleic acid motifs
P. gingivalis co-activates TLR2 and C5aR in neutrophils and the resulting crosstalk leads to E3 ubiquitin ligase Smurf1-dependent ubiquitination and proteasomal degradation of MyD88, thereby inhibiting a host-protective antimicrobial response.
The accumulating data suggest that DCs are necessary, but not always sufficient, to initiate the priming of naive CD4 T cells and the initial commitment of the primed T cells to the Th2 developmental pathway
The proteins relevant to complement activation beginning with ICs in the classical pathway are shown
Signaling pathways employed by CSCs: Distinct combinations of paracrine and juxtracrine signals induce the EMT in different contexts
Three Wnt-dependent pathways have been categorized: canonical Wnt/β-catenin and non-canonical Wnt/PCP as well as Wnt/Ca2+ pathways
Influence of canonical Wnt signals on the MAPK pathway
Influence of non-canonical Wnt signals on the MAPK pathway
Influence of MAPK signals on the Wnt pathway
EphA2 and EphA3 promote cancer stem cell self-renewal, possibly through inhibition of Erk signaling in glioblastoma stem cells
Several microRNAs have recently been described to play a role in the cell fate outcome, survival or apoptosis, under conditions of endoplasmic reticulum (ER) stress
Key events in SR activation signaling are diagrammed on the left; lifestyle transitions that affect SR signaling are diagrammed on the right
TrkA, TrkB, and TrkC isoform expression and activation
LOX-1 on both vascular endothelial cells and DRG neurons will bind oxLDL
Excessive glucose metabolism generates excess NADH and leads to overload of the electron transport chain causing oxidative stress, damage to Mt, activation of PARP
The TGF-β signaling pathway is outlined in thick gray lines, whereas the endosomal recycling pathway and lipid rafts-caveolae degradation pathway are indicated by green and blue lines, respectively
Epithelial-mesenchymal transition (EMT) progression is regulated by signalling pathways that can cooperate to induce full EMT responses
Smad-dependent and Smad-independent TGF-β family signaling
The activation of multiple receptors and complementary pathways are needed
A hypothesis of IPC-induced cardioprotection
Pathway map showing cardiac genes significantly (DE ‚â• 0.950) upregulated (pink) or downregulated (green) compared to controls.
Cytolytic activity of NDV in cancer cells proceeds through direct and indirect mechanisms
Dynamical constraints on a signaling pathway involved in tissue differentiation in rat correlate with allelic variation at the population level in the same pathway in fruit flies, revealing a link between dynamics and evolution
In the absence of a Wnt signal, the destruction complex containing adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK-3β) and casein kinase 1α/ε (CK1α/ε) on an axin-conductin scaffold targets the degradation of cytoplasmic β-catenin in a proteasome-dependent manner
Growth factors binding to their cell surface receptors activate guanine exchange factors (GEF) such as SOS (son of sevenless) that are attached by the adaptor protein GRB2 (growth-factor-receptor bound protein 2)
Regulatory cross-talk between the estrogen receptor alpha and MTA family members
Neurotrophins show ligand specificity for Trk receptors, and activate intracellular signaling cascades, including Ras/ERK, PI3K/AKT, and PLCγ to alter neuronal survival, growth and neuroplasticity
Activated GRs rapidly enhance the translation of Arc and may influence trafficking of TrkB to the membrane surface and/or BDNF release
During early spermatogenesis, primary pre-pachytene piRNAs are produced from transposon and genic transcripts
Retina regeneration requires the activation of a variety of signaling cascades
BRAF oncoproteins promote proliferation by constitutively activating the MAP kinase pathway
Resistance to BRAF inhibitors in metastatic colorectal and thyroid cancers is mediated by loss of a feedback loop (EGF→EGFR signaling in colorectal cancers or NRG1→HER2 and HER3 signaling in papillary thyroid cancers) whereby the MAP kinase pathway activity inhibits mitogen dependent signaling (highlighted in blue)
Multiple mechanisms of acquired resistance (highlighted in blue) to BRAF-V600E inhibitors lead to reactivation of the MEK-ERK pathway (highlighted in red) in the presence of a RAF inhibitor
Cellular signaling through pre-organized and inter-connected nanocluster assemblies with gel-like properties
Signal transduction pathways integrate activity of multiple cytokines
Macrophages produce intracellular cAMP through G-protein-coupled receptor (GPCR)-adenylate cyclases (ACs)
The Hras-Braf MAP-Kinase pathway visualized using GenMAPP software
Cellular insulin and glucose delivery is dependent on insulin transport and diffusion from the intravascular compartment, through the interstitium (a) to the cell membrane where insulin binds to the insulin receptor (IR) and glucose enters the cell via GLUT4
ApoA-I is hypothesized to act on five major pathways to exert its neuroprotective effects pertinent to AD
NADPH oxidase- and mitochondria-derived reactive oxygen species pathways in microglial activation
Glutathione peroxidase activity pathway which was significantly altered in the liver of female LMB, obtained from GSEA, featuring GO terms
Classical Complement Pathway affected in the ovary of female LMB (by gene set enrichment analysis (GSEA))
In the absence of canonical Wnt, cytoplasmic β-catenin is phosphorylated by glycogen synthase kinase 3 (GSK3) and casein kinase 1α (CK1α)
Toll-like receptor (TLR)- or oxidized-LDL (ox-LDL)-induced activation of macrophages leads to transcription of Wnt5a via (a) NFŒ∫B signaling, (b) Ca2+/calmodulin-dependent protein kinase (CAMKII) signaling, or (c) protein kinase C (PKC)- dependent signaling pathways
CTF interacts with a G protein-coupled receptor which activates activates both GŒ±i and Gβγ
Genome-wide microarray analysis was done on tumors from juvenile hosts (n=15) or adult hosts (n=12)
Molecular mechanisms that control AII amacrine cell coupling
Binding of insulin to the insulin receptor (IR) triggers downstream signaling cascades that culminate in GLUT4 exocytosis leading to glucose uptake
EGFR signaling pathways and receptor cross-talk
Left: Yeast nutrient signaling pathway is directly affected by the availability of certain amino acids
Intake of high levels of protein and fats, especially from animal sources has been associated with decreased healthspan in both humans and mouse models
(A) Anti- and (B) pro-apoptotic roles of RIPK1(A) Upon TNFR-1 ligation, RIPK1 stabilizes TNF-R1-induced complex I preventing transition to the pro-apoptotic complex II
(A) Schematic showing signaling interactions between 5-HT1A and GRPR
Model of TACE activation by MAPK signaling
sAC converts ATP in cAMP, the ubiquitous second messenger, which is degraded by phosphodiesterase (PDE)
Schematic illustration of canonical Wnt/β-catenin signaling
Pathways of apoptosis: In response to nitrosative stress either by activation of death receptors (extrinsic) or through the initiation of genotoxic insults that increase pro-apoptotic molecules such as p53 and Bax, the mitochondrial membrane becomes permeable, releasing cytochrome c
PDC selectively express TLR7 and TLR9, which are expressed in the endosomal compartment
A.Genes with altered expression upon miR-224 stimulation are involved in the cell cycle control
Regulation of STEP expression and activity
Mutations in the BCS1L assembly factor cause severe complex III enzyme deficiency, which hampers oxygen consumption and ATP synthesis
Depicted here is the biochemical pathway of hypoxia-inducible factor (HIF) hydroxylation through a combination of α-ketoglutarate (αKG), molecular oxygen (O2), one or more of the prolyl hydroxylase (PHD) isoenzymes and the asparaginyl hydroxylase factor inhibiting HIF (FIH) in normoxia
Inflammatory bowel disease is a result of intestinal inflammation, in which profound changes in metabolic supply and demand lead to an imbalance in oxygen supply
Signaling pathways involving PAN-family proteins
Sex hormone biosynthesis and degradation pathway
A schematic illustration of the mTOR signaling pathway, including major upstream regulators and downstream substrates for both the mTORC2 and mTORC1 kinase complexes
(A) Module 1: Receptor level processes including receptor activation, internalization and recycling
Model of cAMP pathways acting during mammalian sperm capacitation
An example of a cluster illustrating Ras activation
A. A schematic diagram depicting the basic structure of TLX.
Canonical pathway diagram for role of cytokines in mediating communication between immune cells from the IPA Knowledge base is overlaid with gene expression-fold change values at (A) 2 h, (B) 24 h, and (C) 72 h. Green denotes down-regulation, while red denotes up-regulation.
Schematic demonstrating the effects of AMPK signaling in stroke
Growth signals are relayed from activated growth factor receptors to the nucleus
The current model of how Vmem regulates ability of cells to form tumors is as follows []
Activation of HER2/ERK/MKP1 pathway in therapy-resistant breast cancer cells
Central LepRb expression sites and related neuronal circuits
Classic HPE-related pathways that signal predominantly at the ventral midline are shown in orange
(A) After synthesis Notch receptors are cleaved by a Furin-like convertase in the trans-Golgi (S1 cleavage) to produce heterodimeric receptors containing an intra- and extracellular domain
Overview of cardioprotective signaling by ischemic and pharmacologic pre-conditioning (PC) and post-conditioning (PoC)
SIC is generally thought to be initiated by the activation of the cardiomyocytes receptors for LPS (Toll-like receptor, TLR) and cytokines, such as TNF (TNF-R), IL-1 (IL-1R) and IL-6 (IL-6R), among others
The cofilin pathway is activated in tumour cells by stimuli in the microenvironment, such as epidermal growht factor (EGF), detected by the EGF receptor (EGFR) and an unidentified subunit of the ErbB family, which could be either ERBB2 or ERBB3
a | In vivo studies in tumour cells indicate that EGF-stimulated phospholipase Cγ (PLCγ) hydrolyses phosphatidylinositol-4,5-bisphosphate (PIP2), causing the release of active cofilin locally from its complex with PIP2 in the plasma membrane
This figure shows the VEGF pathway for angiogenesis
Glucose-TOR-E2Fa signaling regulates the G1 to S transition and promotes cell cycle initiation in meristems
NOD2 interacts directly with intracellular bacterial PGN fragments containing the MDP motif
HDACs regulate expression of homeobox transcription factor HoxA9, which regulates the expression of endothelial-committed genes in progenitor cells, including endothelial nitric oxide synthase (eNOS), VEGFR2, etc., promotes endothelial cell differentiation and neovascularization.
The complement system is activated through three distinct pathways: the classical pathway, the mannose binding lectin pathway, and the alternative pathway
KEGG pathways significantly associated with NPG
Butanonate metabolic pathway (KEGG pathway hsa00650)
(A) The Wsp signal transduction pathway. A TCS used by the Wsp system co... (B) The Chp signal transduction pathway. Two CheY homologs PilH and PilG...
The selective autophagy cargo receptor p62/SQSTM1 functions as a positive regulator of multiple tumor promoting pathways
eNOS: Endothelial nitric oxide synthase; GPCR: G protein-coupled receptor; NO: Nitric oxide; PIP: Phosphatidylinositols phosphate
Downstream of each receptor, distinct signalling pathways have specific functions in proliferation and recombination
The myeloid differentiation factor 88 (MyD88)-dependent pathway of Toll-like receptor signalling involves Toll/Interleukin-1 receptor (TIR) dimerization between the receptor and the MyD88-adaptor-like protein (MAL)
Upon exposure to antigen and the proper interleukin milieu, CD4+ Th0 cells commit to either the Th1 or the Th2 lineage
Stimulation of the IL-33/ST2 system might activate a cardioprotective programme in the context of ventricular biomechanical stress, and a number of approaches could be taken to modulate IL-33/ST2 signalling to capitalize on this cardioprotective activity
Red lines represent the metabolic cycle for complete acetyl-CoA oxidation including the glyoxylate shunt enzymes, which are shaded orange
After androgen withdrawal, ET-1 enhanced c-Myc expression, via activation of Src and PI-3 K signaling, leading to increased level of AR transcription
Model for signal transduction mechanisms regulating early, adhesion-independent, and late, adhesion-dependent neutrophil ROS generation
(A) In Tregs, TCR and IL-2 signaling promotes Treg proliferation and fun... (B) In conventional T cells, mTOR signaling inhibits Foxp3 induction par...
Depicted are schematics of PDGFR-Œ±, MAPK and NF-Œ∫B signaling pathways as well as downstream effects and resulting cell activities
Simplified schematic of the crosstalk between UPR and proteasome-mediated protein degradation is shown
The proposed biosynthetic pathway of diphthamide
PI3K-AKT-mTOR signalling pathway and associated hamartoma/overgrowth syndromes (PI3K subsumes PIK3CA and PIK3R2, AKT subsumes AKT1-3)
Despite the similarity between IL-17R and TLR/IL-1Rs, studies of IL-17 have revealed several differences in how IL-17R operates
Alterations of the Smad dependent TGF-beta pathways in Cancer
Antigen-presenting cells (APC) take up antigens (Ag) released from cancer cells and present to T cells
In response to growth factor binding to their receptors, the PI3K/Akt pathway is activated, leading to inhibition of GSK-3
The biosynthesis of type I collagen and other fibrillar collagens can be divided into intracellular (parts a–c) and extracellular (parts d–f) steps
Aβ1‚Äì40 (Aβ) activates the innate immunity receptor CD36 leading to production of superoxide via NADPH oxidase
Membrane dynamics and the endocytic pathway
Schematic diagram describing Src regulation by trafficking
Notch and Eph / ephrin signaling pathways of non-myelinating oligodendrocytes relative to corresponding ones of their myelinating counterpart
Signal transduction pathway of bitter (T2R), sweet (T1R2/3), and umami (T1R1/3) GPCRs in type II taste cells of the tongue
Hypothetical model for the formation of localized domains of PI3K-Rac1 signaling that determine sites of neurite formation from the cell body
After initial infection of oropharyngeal epithelial cells (a) EBV primarily infects na√Øve B-cells (b) and subsequently the infected B-cells are growth transformed (latency III), expressing the full repertoire of latent antigens (c)
Schematic of regulation of Wnt canonical and calcium-dependent pathway molecules in microstructured Ti surfaces
LPS stimulates TLR4 which recruits the adapter proteins MYD88 and TRIF to facilitate downstream transcriptional regulation such as cytokine expression
Differentially expressed genes in the important signaling pathway and their connectivity while emphasized into metabolic disease and disorders in the 45 month PCBs exposed population in Slovakia between genes expressed (with ‚â•1.5 fold change, t-test, p <0.05) in a cellular level with some downstream effects, e.g.
A virtual cross section through the vertebrate embryo (zebrafish) with Bmp (A), Hedgehog (B), Vegf (C), Notch (D), non-canonical Wnt/Notch (E), and canonical Wnt signaling requirements depicted (F)
Proposed dysregulated miR-125b-1 signal pathway involved in SCC
A. DIII/IV regions of Aux/IAAs and ARFs are homologous and the DIII/IV of most Aux/IAAs and ARFs form a PB1 domain that comprises both an acidic (+) and a basic (‚àí) faces.B.
Schematic representation shows the function of angiogenic molecules during cerebral ischemia
E2signaling through membrane-associated ERŒ±36 activates two pathways, mediating the proliferative effect through a G-protein-PLC-PKC specific pathway and the anti-apoptotic effect through PLD-LPAPI3K specific pathway
Schematic diagram demonstrating the role of RKIP in the regulation of tumor cell drug/immune resistance (black lines)
Keratinocyte mediators activate MITF which induces expression of enzymes for eumelanin production
A) Recent studies describe a complex network of cell-cell signaling that controls the spatiotemporal pattern of RD gene expression during eye development
Hypothetical model for cross-talk of PI3K/AKT with HIV-1-induced STAT1 signaling
The central role of NMPRTase (Nampt*) in the salvage pathway for NAD biosynthesis and related cellular functions
Canonical WNT signalling regulates mesenchymal stem cell fate
Regulation of protein synthesis through the mTOR signaling pathway by amino acids and insulin
HIV-1 Tat interacts with LRP leading to Src-dependent potentiation of the NMDAR and activation of the NOS/sGC/PKG signaling pathway
Schemes of metabolite 13C labeling patterns as a result of [U13C]glucose (Panel A) or [U13C]AcAc (Panel B) infusions
a | As indicated, for oncogenic F-box proteins, inhibitors that directly block SKP1–cullin 1–F-box protein (SCF) E3 complex formation or inhibit E3 interaction with substrates could be used as anticancer drugs
The COX-2 pathway plays a critical role in angiogenesis, inflammation and cancer ()
As proposed in , two sets of uterine Tregs could be generated during pregnancy
eHsp90Œ± initiates ERK signaling, herein demonstrated via MMP-2/9 activation
Ligand binding induces dimerization, leading to activation of the intracellular tyrosine kinase
Toll-like receptor (TLR), nucleotide-binding oligomerization domain (NOD)-like receptor (NLR), and retinoic acid-inducible gene (RIG-I)-like receptor (RLR) signaling
The phosphatidylinositol 3-kinase (PI3K) pathway regulates cancer cell growth and survival
Upon binding ligand, receptor-associated JAKs become activated and mediate phosphorylation of specific receptor tyrosine residues
A multiplexed luciferase reporter and biochemical platform for fingerprinting molecular libraries
Hormones (insulin) and growth factors (IGF-1) signal through the PI3K/AKT pathway
Cytosolic nucleic acid pattern recognition and activation of ISGs
Two chemical genetic strategies have identified small molecules that inhibit Wnt signaling
(A) miRNA precurso... (B) interact with... (C) These transcri... (D) the repression... (E) cleavage of ho... (F) Exogenously in... (G) tiRNAs and spl...
Binding of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), or other as-of-yet unidentified ligands to pGC-A or unknown ligands to pGC-G induces the conversion of GTP to cGMP by the particulate guanylyl cyclases
Metastasis occurs through a series of stages: local invasion, intravasation, extravasation and colonization (as indicated by the blue boxes)
(a) Activation of PRRs by M.tb and... (b) Negative regulators of macroph... (c) Regulation of macrophage micro... (d) Impact of macrophage lipid med...
(A) TGF-β pathw... (B) Prostate ca... (C) Activation... (D) Activation... (E) Intratumora... (F) Loss of the... (G) Aberrant Y5... (H) Epigenetic...
a | Tadpole-to-adult intestinal epithelium remodelling during Xenopus laevis morphogenesis
A| Ductal elongation and branching of the mammary and submandibular glands
Schematic of Hedgehog (Hh) signaling in Vertebrates
Combined inhibition of PKCι and Hh signaling inhibits the CSC phenotype
Regulation by zinc of the ERK1/2 signaling cascade
Diagram of the proposed signalling pathway involved in the cardiac remodelling process in the absence of natriuretic peptide receptor-A (NPRA)/cGMP signalling
Schematic of rapid membrane receptor mediated mechanisms for enhancing memory by estradiol
Drug targets downstream of receptor tyrosine kinases involved in synovial sarcoma (RTK)
In normal gastric epithelial cells, TFF1 activates PP2A leading to dephosphorylation of AKT, activation of GSK3β, and degradation of the β-catenin protein
Transforming growth factor-β (TGFβ) regulates up-regulation of TWIST1, SNAIL1, and SNAIL2 via the SMAD signaling pathway
A regulatory commonality between differentiation of adipocytes and that of HSCs
Oxidizable substrates are highlighted by yellow boxes
In response to ligand binding a stimulation signaling can occur via G-protein-mediated pathway terminated by subsequent GRK/arrestin binding, or/and via β-arrestin-mediated pathway
(A) CXCL12 is highly expressed in tissues like lungs, liver, and bone ma... (B) Schematic diagram of CXCR4/CXCL12 signaling pathway.
A: Both ligands and receptors are single-pass transmembrane proteins com... B: The receptor is activated in a juxtacrine manner through its interact...
Ethanol (EtOH) is subject to metabolism by catalase (CAT), cytochrome P450 isoform 2E1 (CYP2E1) and alcohol dehydrogenase (ADH)
Differentially expressed gene enrichment of the top scored pathway maps
(A) The genotoxic effects o... (B) The presence of gut com... (C) cyclophosphamide (CTX) (D) total body irradiation... (E) Treatment of mice with...
Opposing effects of glucagon and insulin on the cyclic AMP-responsive element (CRE)-binding protein (CREB) pathway
SF-induced alteration of common metabolic pathway in liver of 24 h rats
Initiation of the TGF-β signaling cascade occurs upon ligand binding to TβRII and subsequent TβRI-TβRII hetero-tetrameric complex formation
Thiamine is absorbed in the intestine and transported by high-affinity thiamine transporters encoded by the SLC19A2 and SLC19A3 genes inside the cell, where it is converted to thiamine pyrophosphate (TPP) by the cytoplasmic enzyme thiamine pyrophosphokinase (TPK1)
Multiple signaling pathways are important in uveal melanoma, but Protein Kinase C and MEK have been identified as points of therapeutic intervention in GNAQ/11 mutant disease
mGluR1/5 signaling pathways relevant to protein synthesis
TLR4/NF-Œ∫B signalling pathway and TLR4/ MAPK signalling pathway in gastrointestinal epithelium
Post-transcriptional gene suppression mediated by miRNAs is involved in the fine-tuning of epithelial anti-Cryptosporidium defence
TGF-β1 ligand-binding initiates signaling events resulting in the activation of SMAD2/3/4 (canonical pathway)
A TGF-α-IL-1α/β-IL-1ra autocrine cascade contributes to TNF-induced hepatocyte proliferation and Adv-infection sensitized apoptosis through the regulation of multiple shared signaling pathways
The blue rectangle on the top represents neural cells while the black rectangle on the bottom represents endothelial cells
Key signaling pathways involved in nicotine plus HFD-induced hepatocellular apoptosis
By transcriptional upregulation of TIGAR, p53 increases the flux of glucose to the PPP
This sketch graph shows potential mechanisms of ketamine-induced changes of the neurogenesis of NSPCs, based on current studies
Described are the upstream and down-stream stages of this pathway in hypoxic and extracellular adenosine-rich microenvironments of inflamed and cancerous tissues ()
The shown anti-hypoxia—A2-adenosinergic drugs exist since fortuitously they have been developed for other therapeutic indications
Different body sites are colonized by diverse groups of fungi, and the communities are shaped by the characteristics of each environment
Notch receptors (Notch1-4) and ligands (DLL1, 3 and 4, Jagged 1-2) are expressed in tumor, normal, and endothelial cells
The pRb/E2F pathway regulates cell cycle progression
Hypothetical model of the functions of the peripheral lamina and the nucleoplasmic LAP2Œ±-lamin A/C complex in the regulation of the pRb/E2F pathway in non-proliferating and proliferating cells
Pathogenesis of HCC and targets for chemopreventive agents
Theoretical model for metabolism of alcohol in the brain
The nutrient signalling network comprised of IIS and TOR signalling pathway in four model organisms (from left): the yeast Saccharomyces cerevisiae, the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the mouse Mus musculus
(a) The overlap of 16p11.2 genes (left Venn diagram) and their co-expres... (b) Comparison of spatio-temporal networks across different brain region...
Schematic of how p-CREB acts as a common downstream effector for multiple signaling pathways that regulate BCRP mRNA expression Xie, et.al
Schematic representation of antiviral pathways in the nematode C. elegans, insects and mammals.
Exposure to hydrophobic BAs induces oxidative stress through ROS generation and further activates TNFŒ±-mediated signaling
17 post-translational modification sites that impact PR-mediated transcriptional action
The uterine endometrium is stylized in this figure, with predominant signaling pathways represented during the proliferative follicular phase of the menstrual cycle (above dotted line) and during the differentiation of the luteal phase (below dotted line)
The physiologic skin pigmentation response (tanning) begins with exposure to UV radiation, which causes DNA damage and thus upregulates p53, leading to POMC transcription in keratinocytes
Through various processes hESCs give rise to neural precursors
Magnetic resonance spectroscopy (MRS) studies with cells, animal models and human studies have revealed deregulated choline metabolism in cancer
Oncogenic signalling pathways (part a) that interact with the choline metabolic pathway (part b) are shown
Enzymes shown in grey indicate active choline cycle enzymes, which are shown in the organelle in which they are active
Inflammasome activation and cross-talk between endothelial cells (ECs) and macrophages (M√ò) in atherogenesis
Upon ER stress, IRE1 is activated by autophosphorylation and oligomerization
Upon ER stress, ATF6 disassociates from GRP78 and translocates to the Golgi apparatus, where it is cleaved by proteases
(A) Schematic of the IL-6–IL-6R–STAT3 pathway a... (B) Cells were stained with anti-hMSH3 antibody... (C) Total cell extract was fractionated into cy...
Signaling pathways regulated by SHP2.SHP2 binds to receptors and adaptor proteins and facilitates positive signaling to multiple signaling pathways involved in important cellular pathways that control proliferation, migration, differentiation, growth, and survival
Hypoxia inhibits prolyl hydroxylation of HIFŒ±, which leads to its stabilization and activation as a heterodimer transcription factor with HIFβ
Autophagy is initiated by encapsulation of cytoplasmic components (proteins and organelles) within isolation membranes to form autophagosomes
Schematic of Wnt/β-catenin and Notch signaling pathways and pathway crosstalk as illustrated herein
(A) The structure of the FGF receptor (FGFR). (B) FGFs signal through receptor tyrosine kinas... (C) Proposed model for the different epithelial...
In the absence of Wnt ligands (Wnt OFF), cytosolic β-catenin that does not participate in adherens junction (AJ) stabilization is captured by the destruction complex, where it is first phosphorylated, and then ubiquitinated by recruiting β-TrCP followed by its proteasome-mediated degradation
A, B Canonical Wnt pathway; C, D Noncanonical Wnt pathway
Retinol (ROL), bound to RBP4 binds to its receptor STRA6 in the cell membrane
(A) Schematic representation of EndMT regulated by different signaling pathways
Schematic of PI3-K-AKT signaling pathway
(A) Inflammation. HIF-1α and NF-κB... (B) Infection. HIF-1α increases in... (C) Cancer. As a result of hypoxia... (D) Metabolism. HIF-1α in myeloid...
The recruitment of myeloid cells to atherosclerotic plaques represents a critical process in the initiation and progression of atherosclerosis
A) Diagram of the preparatory and pay-off phases in glycolysis. The prep... B) The glycogen shunt hypothesis. Glycogenesis: The PGM, an isomerase, s...
A. Regulatory factors involved in nuclear miRNA processing are summarized as indicated.
Schematic representation for the role of Œ±-toxin in the inhibition of macrophage apoptosis by S
(A) Schematic representation of the sphingolipids metabolic pathway. (B) The different biological functions downstream of S1PR2.
Molecular events in the autophagy pathway
Pathway analyses of direct interactions among transcripts mediated by P4 in the ovary
Pathway analyses of A) tumor protein p53 (TP53) B) E2F transcription factor 1 (E2F1), and C) miRNA 124-1
Canonical NF-Œ∫B, a homodimer of p65 and p50 proteins, is cytoplasmic and inactivated by IŒ∫B proteins
The model shows that β1 integrins enhance downregulation of Egfr signaling through endocytosis
Pathway for the synthesis of the endocannabinoids AEA and 2-AG
The mTOR pathway is regulated by numerous upstream pathways, typically in response to growth factors (anabolic) or energy/nutrient deficiency (cell static or catabolic)
(A) Glutamate homeostasis i... (B) After chronic cocaine,... (C) Cartoon of PFC-NAc path... (D) Stress, cues, or drug p... (E) Interfering with impuls...
P. gingivalis co-activates TLR2 and C5aR in neutrophils, and the resulting crosstalk leads to E3 ubiquitin ligase Smurf1-dependent ubiquitination and proteasomal degradation of MyD88, thereby inhibiting a host-protective antimicrobial response.
P. gingivalis interacts with the TLR2/1 receptor complex, whereas it evades or antagonizes TLR4 by expressing atypical lipopolysaccharide structures (with non-phosphorylated tetra-acylated lipid A or mono-phosphorylated tetra-acylated lipid A, respectively).
Pathway names are indicated in bold and situated in the cellular context in which they function
Schematic shows regulation and expression relationships between genes related to canonical SMAD signaling after burn injury
. G-protein Œ±s-subunits (GŒ±s) signaling pathway.
RAS-mutant cancer cells are characterized by increased macropinocytosis and uptake of albumen, leading to lysosomal degradation and release of amino acids
Cancer stem cell (CSCs) are metastatic cancer cells that can self-renew
Simplified version of intracellular MEK/ERK and AKT/CREB signaling pathways that affect SMN transcription, including the upstream regulators (NMDA, EGF, FGF, PDGF and BDNF)
In glomerular podocytes, mitochnodrial dysfunction elicited by oxidative stress is an early event associated with aldosterone-induced podocytopathy likely via the non-classic mineralocorticoid receptor (MR)
Two main chaperone systems, the lectins CNX/CRT (a) and the Hsp70 chaperone BiP (b), aid the folding proteins for secretion (c) or if folding fails, target them for ERAD (d)
miR-21 downregulates pro-inflammatory response via blocking the TNFŒ±-NFŒ∫B pathway, and upregulates anti-inflammatory IL-10 via the AP-1 pathway
Activation of RTKs and downstream signaling cascades
Oncogenic ras-induced senescence is mediated by sequential activation of the Raf- MAPK/extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinases (ERK) and mitogen-activated protein kinase kinase (MKK)3/6-p38 pathways
Pathway 1: VV infects immature and/or mature DCs which travel to draining lymph nodes and express co-stimulatory proteins and MHC class I/PSA (1a) where they trigger activation and proliferation of PSA-specific CD8+ T lymphocytes (1b), which then circulate to tumor sites and kill tumor cells through programmed cell death (PCD) (1c)
Pathway diagrams depicting the percentage of samples with alterations in3A - RAS/RAF/MEK/ERK and PI3K/AKT signaling3B - cell cycle, and3C - squamous cell differentiationAlterations are classified as activating (high-level amplification or known activating mutation colored red), inactivating (homozygous loss or truncating mutation colored blue), or potentially cancer associated (COSMIC mutation colored white)
A Model of the pro- and anti-inflammatory functions of pulmonary collectins in macrophages
Gene Ontology and pathway categories that are enriched (P≤0.01, Fisher's exact test) in misregulated genes from ASD cases compared to controls were identified (n=18), along with the corresponding set of genes from ASD cases.
LTP at both synapses mostly containing CI-AMPARs has a strong dependence on presynaptic activation and rise in postsynaptic calcium levels
Our working model illustrated that sequential release of pro-inflammatory factors suppresses later IL-10 production in LPS-stimulated microglia
An extended signaling pathway that regulates basal P-glycoprotein activity at the blood-brain barrier
A schematic model illustrates that temozolomide (TMZ) triggers loss of K+i, Cli and apoptotic volume decrease (AVD), and leads to apoptotic cell death in glioblastoma cancer cells
Mouse models with defects in OXPHOS complexes subunits, electron carriers and assembly factors are summarized in the figure
(A) Basal transmission: the synaptic response, evoked by low-frequency stimulation, is due to glutamate activating AMPARs in the ACC
This model shows an interrelation of pathological hallmarks in sporadic inclusion body myositis (sIBM) including vacuoles, muscle atrophy, degeneration, accumulation of protein aggregates, and inflammation (shown in boxes)
Shown are: (1) ADO-PGE2pathway; (2) the neuropilin1-semaphorin4a pathway; (3) the TGF-β pathway; and (4) the IL-2/IL-2R pathway
Signal transduction pathways from the cell membrane to the nucleus discussed in this article
We developed a model of the cholera-related immune pathways under selection in the BEB population by mapping all interactions cataloged by Ingenuity’s IPA software between strongly selected genes, including IKBKG, and genes shown to respond to cholera toxin (see methods)
Intracellular signaling proposed to be involved in the inflammatory response during immune-mediated joint diseases such as aseptic loosening
Simplified overview of the RA-associated inflammation-promoting factors
Model of chemoattractant signaling pathways in Dictyostelium discoideum
Canonical Rho GTPase signaling motifs regulate actin cytoskeletal dynamics
Schematic diagram illustrating intracellular signaling pathways in a macrophage involved in cytokine regulation by adrenergic and cholinergic agonists and receptors following lipopolysaccharide challenge
The serum response factor pathway in myelopoiesis and myelodysplasia with 5q abnormality
Working model of signaling pathways to hypoxia-induced phrenic motor plasticity
CBA returning from the intestines following a meal activates S1PR2
Bile acids are the end products of cholesterol catabolism
Schematic representation of the role of T cells in the anabolic activity of iPTH in trabecular bone
Molecular pathway representing downstream deregulated molecules involved in regulation of cell cycle progression and cellular proliferation associated with IR injury at early post-LT
Cytotoxic cells kill the target cells by one of the two mechanisms
a | microRNAs (miRNAs) that promote neurogenesis are often integrated into positive transcriptional and epigenetic feedback loops
A, In diabetes, hyperglycemia triggers mainly increased ROS production through eNOS uncoupling and PPP impairment resulting in stalled glycolytic flux with glycolytic intermediates being diverted into alternative metabolic pathways leading to additional excess ROS and AGEs production
A. Complement activation on diseased host surfaces involves diverse recognition molecules and initiation mechanisms that underlie three distinct activation pathways operating either in parallel or independently of each other.
A schematic illustration of the current concepts of mechanism by which adjudin perturbs apical ES function in the seminiferous epithelium to induce germ cell loss from the seminiferous epithelium
Antibody therapy activates complement through the classical pathway, with subsequent amplification through the alternative pathway, and complement regulators (red text) act on many levels
Cellular insults activate the DDR, which consists of multiple signaling pathways that ultimately lead to cell cycle arrest, DNA repair, or apoptosis
IL-10 signaling pathways in normal and abnormal conditions
Integrins can paradoxically initiate pro-survival as well as pro-apoptotic signals
Integration of the 3 major pathways that regulate skeletal muscle mass
The interplay between multiple factors in the transforming growth factor-β (TGF-β) signalling pathway and the control of muscle mass
(A) Canonical Wnt Signaling. Without activation of the Wnt ligand, β-cat... (B) The interaction of aspirin with Wnt signaling. Aspirin interacts at...
(A) Complement activation is effectively contained on the surface of nor... (B) Lack of GPI-linked CD55 and CD59 leads to the functional ‘dismantlin...
(A) Simplified schematic overview of the complement cascade illustrating... (B) Benefits and limitations of complement-targeted therapeutic strategi...
Interferon (IFN) signaling via the JAK–STAT pathway
Induction of interferon (IFN) and its antagonism by viral proteins
(A) Molecular contexts dictating applications for isoform-selective PI3K inhibitors
When the Hippo pathway is activated, MST1/2 in complex with SAV1 phosphorylate and activate LATS1/2 and MOB1
External signals including antigen, costimulation, nutrients, cytokines and metabolic cues converge upon PI3K signaling pathway that results in the phosphorylation and activation of Akt (threonine 308) leading to further downstream activation of two distinct mTOR containing signaling complexes namely mTORC1 and mTORC2
(A) Innate immune cells such as DCs dependent upon glycolytic metabolism... (B) to generate immunomodulatory signaling cascades (such as cyclic AMP...
Mammary gland epithelial cells form polarized acinar structures when cultured in 3D matrigel
Probable sulfoquinovose biosynthesis pathway in S
In human melanoma A375 cells, where B-RAF is constitutively active, IGF1R signals mainly through the IRS1/2-PKB axis, inducing cellular survival and proliferation
The expression of the known genes involved in polo signaling in PAH HPASMC
The figure shows the two major routes for glutamine metabolism in mammalian cells, glutaminolysis and reductive carboxylation
Proliferating tumor cells deplete critical nutrients such as tryptophan (Trp) or glucose
Five main mechanisms have been proposed for how PD-1 modulates T cell functions
Overview of TLR/IL-1R, RLR, cGAS, and inflammasome signaling pathways
(left) On pro-integrin clustering surfaces, which could be either smooth or composed of certain nanotopographical features, integrins could undergo free lateral recruitment and ligation with ECM proteins, and thus cluster and form mature, stable FAs together with the unhindered recruitment of FA adaptor proteins
Molecular pathway of glycolysis in NSPCs
Overexpression of API5 upregulates FGF2 and FGFR1 signaling
Schematic representation of reported interactions between factors associated with Peters anomaly
Canonical and noncanonical NLR inflammasome activation
Regulation of lymphatic muscle contraction occurs primarily through phosphorylation of the 20-kDa regulatory myosin light chain (MLC20), which is regulated by the relative activities of MLC kinase (MLCK) and MLC phosphatase (MLCP)
Inhibition of the classical apoptosis and autophagy pathway by γ-herpesvirus proteins
Activation of the NLRP3 inflammasome is a two-signal process
Gene network analysis for 18 key genes involved in age-dependent tumor progression
Diagram of EGFR signaling pathway showing impact of gefitinib and erlotinib on EGFR downstream signaling proteins
High extracellular Ca2+ from necrotic cells activates CASR and GPRC6A
Daam2 associates with PIP5K and promotes the clustering of Wnt receptor complexes into signalosomes through PIP2
This diagram describes some of the major pathways responsible for rodent β-cell proliferation
Proposed schema of aberrant signal transduction mediated by the TSLPR heterodimer in CRLF2-overexpressing ALL
These network models show the predicted strength of relationships between all known FGF signaling ligand-receptor pairs []
Analogously to , species-specific predictions are shown for a portion of the KEGG pathway map for JAK/STAT signaling focused on the IL-6 family of cytokines
Our data suggest that Carma1 and MALT1 participate in the TCR-dependent activation of mTOR downstream of PKC
Dependence on signaling pathways based upon tumor suppressor status
Pathway of all possible EGFR family dimer combinations showing various growth factors known to activate EGFR family and all possible dimer combinations
Single and combinatorial treatments of inhibitors were added to rat OPCs upon the addition of T3 and cells were collected 1 day post treatment
Binding of the putative ligand to cytokine receptors leads to receptor dimerization and approximation of two JAK2 molecules, which trans-phosphorylate and activate each other
ROS are important contributor to renal injury and inflammation
Activation of TGF-β requires liberation of the TGF-β dimer from an inactive latent complex with the LAP (see text)
An example of positive and negative regulation of the Ifn-signalling pathway
The adipocytokine signaling pathway as represented in the Kyoto Encyclopedia of Genes and Genomes (KEGG; http://www.genome.jp/kegg/kegg1.html) (; , )
Vitamin D signaling via vitamin D receptor (VDR) and retinoid X receptor (RXR) regulates the transcription of numerous genes involved in carcinogenesis through effects on inflammation, cell proliferation, differentiation, apoptosis and angiogenesis
Diagram depicting altered mRNA expression of molecules involved in the regulation of the actin cytoskeleton by NMDA signaling pathways in schizophrenia
Diagram depicting molecules involved in actin cytoskeletal regulation mediated by NMDA signaling pathways and having altered mRNA expression in bipolar disorder
Model for sex-specific regulation of mitochondrial maintenance pathways
Atherosclerotic plaques begin with the recruitment of inflammatory cells such as monocytes and T cells to the endothelial lining of the blood vessel
A, T cell receptor (TCR) and CD28 costimulatory signals are important for induction of Foxp3
β-Catenin immunohistochemistry in normal adult mouse liver
Canonical, Noncanonical, and Endoglin/ALK-1 signaling pathways
A. Oligosaccharide Glc3Man9GlcNAc2 (G3M9) is transferred to Asn residues on nascent polypeptides by oligosaccharyltransferase.
Ligation of HLA molecules by high titers of anti-HLA antibodies stimulates EC proliferation by upregulating fibroblast growth factor receptor (FGFR) expression, increasing FGF ligand binding and activating the ERK signaling pathway
Ligation of HLA molecules by low titers of anti-HLA antibodies activates Rho and Rho kinase and stimulates phosphorylation of Src and focal adhesion kinase (FAK) followed by downstream activation of the mammalian target of rapamycin complex 2 (mTORC2) pathway culminating in increased expression of cell survival proteins
The PGR operates via multiple signaling pathways within the cell
So far, induction of apoptosis is the predominant route of HDACi-induced cell death
The role of albumin overload in tubular epithelial cells
We propose three possible pathways that could lead to liver NKT cell anergy
Non-canonical Wnt signaling is defined as Wnt/Frizzled (Fz) initiated signaling independent of β-catenin transcriptional function
Simplified TAM signaling pathways in supporting cell proliferation and survival (A) and inhibiting inflammation (B)
Arginine deiminase (ADI) hydrolyzes arginine into citrulline
Oxidative stress activates ASK1 signaling pathway
In contrast to cell-free virus infection, the virological synapse can promote the entry of multiple HIV virions into target cells [, , , ]
Signaling pathways deregulated in HPV-associated HNSCC
RPPA analysis in HeyA8-MDR treated with ZA
The S. pombe glucose/cAMP signaling pathway presented using the ProteinLounge Pathway Builder Tool.
Summary of the HGF/c-Met signaling pathway
(A–C) The LGV C. t central carbon metabolic network.
Cellular and signaling pathway view of gene expression changes during alcohol withdrawal
a| The Kaposi's sarcoma-associated herpesvirus (KSHV) anti-apoptotic protein viral FLICE-like inhibitory protein (vFLIP) activates nuclear factor- Œ∫B (NF-Œ∫B) signalling by targeting NF-Œ∫B essential modifier (NEMO), which is a central regulatory subunit of the upstream inhibitor of NF-Œ∫B (IŒ∫B) kinase (IKK) complex
As the bacterial load of P. gingivalis in the oral cavity increases Periodontal Disease becomes more severe.
Model of Kreb's cycle used to determine relative flux rates through acetyl-CoA synthetase (ACS), pyruvate dehydrogenase complex (PDH), pyruvate carboxylase (PC), and glutamate dehydrogenase (GDH)
Farnesoid X receptor (FXR) regulates enterohepatic circulation of bile acids
Farnesoid X receptor (FXR) regulation of hepatic glucose and lipid metabolism in liver, adipocytes, and intestine
(A) Rb regulates multiple cellular processes, i... (B) NS5B interacts with Rb in the cytoplasm of... (C) Ubiquitylation targets Rb for proteasome me...
A: PC1 and PC2 are found on the plasma membrane (PM) in this model. Acti... B: Polycystins signaling through the primary cilia. Renal cilia bend in...
Insulin resistance associated with obesity, especially central, occurs due to pre-receptor, receptor and/or post-receptor impairments, mainly secondary to elevated FFA, hyperinsulinemia and increased cytokines
HLA crosslinking by antibodies of any subclass causes intracellular signaling leading to endothelial cell (EC) activation
(A) Macrophages perpetuate activation and recruitment via complement and... (B) Recent studies have identified a novel role for endothelial cells an...
Filoviruses enter the host cell via micropinocytosis and escape the endosome (depicted as a circle containing a virus)
Receptor-mediated activation of PI3K-Akt pathway and signaling
During gastrulation, early, high BMP levels activate several NB-specifying genes and low BMP levels, controlled by the secretion of BMP antagonists, allow the expression of neural genes (e.g., SoxB1 transcription factors)
Schematic of the fundamental aspects of the DNA damage response pathway
The stars represent proteins identified on LLV matched on the KEGG pathway “Leukocyte Transendothelial Migration” using DAVID software
A schematic summary graph shows that mGluR2/3 agonists reduce glutamate release at presynaptic site by inhibiting AC-cAMP-PKA signaling pathway
A schematic summary graph shows the postsynaptic effects of mGluR2/3 agonists on the regulation of both AMPA and NMDA receptors
TGF-β can signal through both the classical pathway and the non-canonical pathway
A) Epigenetic gains mapped onto Module 10; genes associated with gains are highlighted as in
The WNT–β-catenin signalling cascade has crucial roles in cell fate, proliferation, survival and migration
This figure shows the dichotomous roles of WNT signalling in the expansion and maintenance of potency in stem cells, as well as in the initiation of differentiation and lineage commitment
Schematic representation of the identified epigenetic regulatory mechanism involved in the miR-124/STAT3 pathway in pediatric-UC
Schematic drawing to illustrate the neurochemistry and molecular mechanisms of c-fos and Fos expression in strongly activated neurons in prefrontal cortex and nucleus accumbens of awake behaving animals
Pathway map of the histamine receptor response in dendritic cell
Pathway map of the Prtostaglandin E2 receptor signaling
Ratio heatmaps of identified canonical TCR signaling proteins that showed significant changes of phosphopeptide abundance for both types of stimulation (q value < 0.05; > 2–fold or < 0.5-fold)
Binding of Wnt ligands to frizzled and low-density lipoprotein receptor-related protein 5/6 (LRP5/6) complex leads to attenuation of phosphorylation and stabilization of cytoplasmic β-catenin
A variety of metabolic processes that branch off of glycolysis are dysregulated in diabetes, including the polyol, pentose phosphate, and hexosamine pathways
miRNA biogenesis pathways are emerging as critical components of gene regulatory mechanism controlled by growth factor signaling (and other) pathways
Smad-mediated regulation of miRNAs can be classified into two mechanisms
Parameter estimates from the best-fitting common pathway model for cannabis, stimulant and sedative abuse in Swedish male–male twin and near-aged sibling pairs
Hypothetical involvement of glucokinase (GK) and therefore glucokinase activators (GKAs) in the preservation and growth promotion of pancreatic β-cells
D2R decreases reactive oxygen species (ROS) production in the kidney by increasing the expressions of HO-2, PON2, and DJ-1 and inhibiting NFŒ∫B activity (NFŒ∫B increases NQO1 expression)
Modulation of surface Fzd density by R-spondin-LGR5-RNF43
Multiple agents have shown the propensity to inhibit various steps of the glycolytic pathway
Notch signaling regulates hepatic glucose production through synergy with FoxO1, which directly activates the transcription of G6pc and Pck1, the rate-limiting enzymes in hepatic glycogenolysis and gluconeogenesis, respectively
In response to cold ambient temperature, sympathetic nervous system releases catecholamine, which binds with β-adrenergic receptor and activates lipolysis through the cAMP pathway
Potential HCC chemoprevention targets are extracted from the broader pathogenic involvement of HCV in the development of hepatitis, fibrosis, and cirrhosis
Adipocyte receptors that have been proposed to promote the browning of white fat or maintenance of a brown adipocyte (BA) phenotype
Illustration of the deformation-induced ATP release pathway, highlighting the importance of glucose metabolism via the pentose phosphate pathway
*Bias-corrected CI from bootstrap analysis
Downstream components of ERK in SCN neurons
The role of p38 MAPK in the circadian clock
The role of JNK MAPK in the circadian clock
Transcriptional regulation of the OS MAPK pathway by the circadian clock in Neurospora
Proteins from known pathways localized to the Trichomonas vaginalis hydrogensome
Innate immune responses are required for allo-ECDI-SP tolerance induction
Schematic of the β-cell exocytosis regulatory system
Both internal and external signals can influence alternative splicing through post-transcriptional modification of specific splicing regulators as illustrated, which may modulate both protein–protein and protein–RNA interactions to produce a network response to affect many regulated splicing events
Our proposed pathway: UVB exposure leads to increased COX-2 expression which results in increased PGE2 production
A. A schematic of the neogenin protein, which has four immunoglobulin (IG) repeats and six fibronectin type III (FNIII) repeats located in the extracellular domain, a transmembrane (TM) domain, and three conserved P1, P2 and P3 motifs located in the intracellular domain.
The initiation and resolution of inflammation is regulated by numerous lipid mediators
A broad array of stimuli can induce an M1 pro-inflammatory response
Upon an extensive amount of DNA damage PARP becomes over activated as a repair response, but in the process NAD+ levels can plummet
Canonical pathways activated in CD14+ monocytes in Behcet’s disease
A model diagram of tumor necrosis factor-alpha (TNF-Œ±) signaling
IL-10 signaling leads to the production of numerous gene products (indicated in red) that are capable of suppressing TLR- and IFNγ-signaling in a variety of ways
A model of the changes in the phosphorylation of TCR signaling components that occurred after inhibition of ZAP-70 catalytic activity (represented by the blue line), illustrated as quantitative SILAC ratio heatmaps beside individual proteins, corresponding to the changes in phosphorylation between the inhibitor-treated and control cells across the four time points of TCR stimulation
While the strength of TCR signaling and the quality of co-stimulation have been demonstrated to influence naïve CD4+ T cell polarization, the cytokine environment largely dictates TH differentiation
A model depicting PPP1R12A/PP1cŒ¥ in the insulin signaling pathway
Slit/Robo interactions and their roles in carcinogenesis
The top enriched network associated with BCa progression
Key components of the Wnt/β-catenin signaling pathway
AMPK is a negative regulator of the Warburg effect in Fumarate hydratase-deficient kidney cancer
Resistance to BCR-ABL1 tyrosine kinase inhibitors may take the form of (left) point or compound mutation-based, BCR-ABL1-dependent resistance or (middle) recruitment of alternative pathway signaling upon effective inhibition of BCR-ABL1
(A) In the posterior midgut epithelium of Drosophila, damaged enterocytes (EC) secrete Upd cytokines upon the activation of stress signaling involving JNK and Yki
A. Each reaction in the network is linked to a protein and encoding gene through the gene-protein-reaction (GPR) relationship.
Acid exposure increases luminal ATP concentration
. Diagrammatic representation of the ORM modulation of the Sonic hedgehog signaling pathway.
Microvessel ensheathment is initiated by BDNF/TrkB signaling, which is regulated by RhoA pathway and is sensitive to RhoA kinase (ROCK) inhibition
RhoA regulates, through its downstream effector ROCK (containing ROCK 1 and ROCK 2 isoforms) actin filament polymerization and organization, which in turn regulate various functions of pericytes
The mechanisms by which β-cell failure an apoptosis occur are complex, not completely unraveled and involve the interplay of numerous factors and conditions
a | The family of extracellular HH ligands, of which there are three in mammals (sonic hedgehog (SHH), Indian hedgehog (IHH) and desert hedgehog (DHH)) bind to the patched 1 (PTCH1) receptor
Binding of Reelin to its receptors, VLDLR and ApoER2, induces SFK activation and Dab1 tyrosine phosphorylation
Protein Cys map to functional pathways based upon percent oxidation
NEDD9 co-localizes and interacts with BCR-ABL and its adaptor protein CRKL [, ], likely serving as a hub [] for an assembly of protein complexes between CRKL and its downstream effectors: SYK [], C3G [], BRAF, SAPK, JNK [], and STAT5 []
NF-Œ∫B is a complex signaling cascade that comprises two separate pathways
mRNAs that were significantly altered in lungs from Klf5Δ/Δ mice were subjected to literature mining to identify potential functional associations and regulatory relationships using Pathway Studio 5.0 (Ariadne Genomics).
Fatty acid remodeling of membrane phospholipid (compartment A)
The Pathway of Net Citrate Production in Prostate Epithelial Cells
Prevalent mutations in acute myeloid leukemia (AML) potentially affect HIF levels in cancer cells
(A) Breast cancer cells can secrete factors, including angiopoietin-like 4, epiregulin, MMP1, and MMP2, which increase vascular permeability and facilitate extravasation by disrupting pulmonary endothelial cell-cell junctions
G protein-coupled PAC1 receptor isoforms within the third cytoplasmic loop
a, Gene interaction map of Reactome pathway analysis that discovers alteration of FGFR signaling as the most altered pathway
Crosstalk between Wnt, PTH and BMP signalling in cartilage and bone cell lineages
Investigational approaches targeting the factors contributing to celiac disease pathogenesis
Adrenergic receptor signaling and cross-talk with the renin-angiotensin aldosterone system
A proposed mechanism by which hyperaldosteronism decreases pulmonary endothelial eNOS activation and nitric oxide (NO‚Ä¢) generation in PAH
More than 90pct of pancreatic cancer (PC) patients have mutations (G12D/G12V) in codon 12 of KRAS that results in its constitutive activation and hyper activation of its downstream signaling pathways accompanied by increased proliferation, motility and survival of PC cells
(A) Binding of TGF-β to its cognate receptor leads to phosphorylation an... (B) In the presence of SHH ligand, the PTCH1-SMO association gets remitt...
Genes were categorized as related when co-cited in the same sentence with a functional descriptor in-between
Insulin binding to the α-chains of the IR triggers pY of the β-chains of the receptor inside neurons
(A) Metabolic labeling of sialylated glycans with Ac4ManNAl leads to the... (B) Metabolic labeling of mucin-type O-glycans with Ac4GalNAz via the Ga...
The pathway of net citrate production in citrate-producing prostate epithelial cells
Summary of altered glucose metabolism in MCF10A-ras cells
Schematic of mechanisms on CYP2J2/EETs mediated macrophage polarization in response to LPS-induced inflammation and cardiac dysfunction
Intracellular levels of BH4 depend on three production conduits the de novo synthesis pathway, the recycling pathway and the salvage pathway
The role of gut microbiota in the development of T1D
Viral protein antagonists of three cytosolic signaling pathways are represented here: 1) TLR3 activation leads to signaling through TRIF, TRAF6/Rip, and IKKŒ±/β to turn on NFŒ∫B
(A) Schematic of viral RNA recognition and antiviral signal activation b... (B) for details.
Combined proteomics and metabolomics data of human RCC tissue was overlayed onto a stylized KEGG-based pathway diagram
Commitment and maintenance of gonadal cell fate
Synapse dysfunction: as a consequence of MAPK and mitochondrial oxidative stress-mediated tau hyperphosphorylation
Ageing is accompanied by changes in cellular processes, impairments in the integration of cellular activities, and deficits in physiological functions
TLRs signal activation of the MyD88-dependent pathway from the plasma membrane (TLR2, TLR4, TLR5) or from endosomes (TLR7, TLR9) to recruit adapter/kinase complexes involving MyD88-IRAKs-TRAF6-TAK1 to mediate activation of NF-Œ∫B and expression of pro-inflammatory cytokines and chemokines
A: In macrophages, TRIF signaling activates TBK1 and IKKe that activate... B: In microglia cells, TLR2 or TLR4 signal activation of TRAF6 via the M...
A: TLR3 exclusively employs TRIF to recruit RIP1 in order to activate TA... B: Upon microbial infection of the gut, bacterial-derived MDP, a compone...
(A) RNA viruses, such as VSV and Sendai virus, and transfected poly(I:C)... (B) Noncanonical NF-Œ∫B pathway is also activated by M-CSF along with ma...
Overactivation of the Ras/MAPK signaling pathway in mutant HRAS (mtHRAS) astrocytes (green) results in both early Ras-specific gliogenesis and an extracellular response, which can be in part reduced by FTI-277 and SNAI2 knockdown
Cyclic AMP accumulates in T cells in the region of lipid rafts in response to TCR activation, and more globally in response to strong Gs-coupled A2AR activation
Pathway for the biosynthesis of NAD+ and poly(ADP-ribose) (PAR) from precursors, showing the chemical structures of the precursors, intermediates, and products, as well as the enzymes catalyzing each reaction (listed in blue text)
A schematic diagram of Notch, InR/Akt, and JNK signaling pathways
Schematic diagram of the VEGF-165—VEGFR-2—Sox18 signaling pathway in differentiating ECs
Cross-species comparison of PCD factors implicated in aging
Schematic diagram of mTOR-mediated T cell activation and lineage specification
Pharmacologically targetable regulatory checkpoints of the mTOR pathway
(A) HCV-infected hepatocytes form clusters (ind... (B) Specific HCV RNA structures are recognized... (C) HCV persists in the presence of ISGs. IFN-β...
Following binding to agonist ligands, Dectin-1 recruits Syk through a phospho-tyrosine in the hemITAM motif
Binding of different ligands results in recruitment of different effectors to the tail of DC-SIGN
Both DNGR-1 and Mincle signal via Syk kinase in response to encounter with necrotic cells
(A) The core knowledge of the Hippo signaling pathway before proteomics... (B) The Hippo signaling pathway refined with newly identified components...
a Structures of schweinfurthin B and 3-deoxyschweinfurthin B (3dSB)
Schematic Representation of BCR Signaling Pathway and Small Molecule Inhibitors of BCR Signaling
The binding of insulin to its cell surface receptor triggers the recruitment and activation of PI3K
In unstimulated cells, a minimal complex of GSK-3, axin, APC and β-catenin is required for GSK-3-mediated phosphorylation of β-catenin which targets it for ubiqitination and degradation
The intestinal enterocyte is a gatekeeper of cholesterol balance with two opposing pathways delivering cholesterol from opposite sides of this polarized cell
Autophagy is modulated by environmental nutrient signals via a signaling pathway dependent on AMP-activated protein kinase (AMPK) and the mammalian (mechanistic) target of rapamycin (mTOR)
Folates provide a backbone for the transfer of one-carbon units
Glycolysis and the TCA cycle are two separate yet connected biochemical pathways that function to generate ATP as well as metabolic precursors for biosynthesis
(A) The AMPK pathway is influenced by adenylate concentration. AMPKα is... (B) α-KG– dependent enzymes (in yellow) are a class of enzymes regulated...
Downstream signaling pathways of the ANG1-7/Mas pathway in non-epithelial lung cell types
Tryptophan (Trp), nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR) are utilized through distinct metabolic pathways to form NAD+
A. NAD+ is an essential coenzyme for sirtuin, PARP and CD38 activity, all of which metabolize NAD+ into NAM.
A speculative model of FGF23 gene transcriptional regulation
Colorectal carcinogenesis follows a stepwise sequence where normal colonic epithelium transforms into adenomatous polyps followed by progression to malignant carcinoma
(a) In the absence of a signal, the destruction complex (APC–Axin–GSK-3–... (b) The binding of Wnt ligand to its Frizzled receptor and LRP5/6 co-rec...
A large number of non-canonical Wnt/PCP signaling pathways have been described
The core Hippo pathway was defined in Drosophila as a cassette composed of the Ste20 family kinase Hippo (Hpo), which forms a complex with the WW domain adaptor protein Salvador (Sav)
Recent studies have uncovered unsuspected cross-talk between the Hippo pathway and other growth regulators
Depicted is the canonical TCR signaling pathway with quantitative J.Vav1 to J.Vav1.WT ratio heatmaps beside individual proteins, corresponding to the changes in phosphorylation between the two cell types across the four time points of TCR stimulation.
Possible pathways of Cd-induced MAPK/ERK signaling
Interaction of the TFF2-CXCR4 axis with the active RAS-RAF-MEK-ERK pathway in the serrated pathway of colorectal cancer
Effect of the combination of rapamycin and resveratrol on the PI3K/Akt/mTORC1 signaling pathway
Proposed Model For the Convergence of Signaling Between mTOR and PPARγ Agonists in Endothelial Cells
Genes that were found in the genomic analyses of SHH-MBs to harbor activating mutations (green stars), inactivating mutations (red stars), or were found to be amplified (MYCN and GLI) are indicated
1. Activation of ER by E2 induces activation AP-1 complex.
The development of dendritic cells (DCs) from progenitor cells is associated with mitochondrial biogenesis, which is driven by peroxisome proliferator-activated receptor-γ (PPARγ) co-activator 1α (PGC1α) and promoted by PPARγ, mammalian target of rapamycin (mTOR) and MYC
In resting dendritic cells (DCs), fatty acid oxidation is engaged and the endoplasmic reticulum (ER) is relatively constrained
The mitochondria-associated membranes (MAMs) are areas of close interaction between mitochondria and the endoplasmic reticulum (ER)
ARDs share molecular pathologies affecting a common signaling pathway involved in activity-dependent protein synthesis in distal dendrites near spine synapses
Schematic representation of the signaling pathway involved in EPO-induced neuroprotection
IL-6 Receptor and gp130 Receptor signaling: IL-6 binds to the IL-6 receptor (1)
Inflammatory blood cells, such as leukocytes and platelets, which are originally from hematopoietic cells in bone marrow, can secrete the hematopoietic lineage, cell-specific micro-ribonucleic acid (miR)-223 into circulating serum
Metabolism and transport of acetaminophen in the liver at highly toxic doses
Oxidative stress induces aberrant signaling pathways
The activity change and interaction of key molecular targets downstream of oxidative stress induced by maternal diabetes
Sensors recognize structures at sites of DNA damage induced by DNA breaks and replication stress
Viral infection and viral gene products (shown outside the gray boxes) activate DDR signaling (shown within the gray boxes) directly or indirectly through induction of ROS and replication stress
TRAIL signaling pathway and some points of therapeutic intervention
Downward traffic of the FSHR is linked to intracellular signaling pathways
Pathway analysis of cytokines determined to be up-regulated in plasma collected from pancreatic adenocarcinoma patients
In normal tissues the expression of MDM2 and p53 are balanced; whereas in HCC cells the balance is disrupted, where the expression of MDM2 can be high and p53 can be low
Berberine activated AMPK negatively regulates the mTOR signal pathway, resulting in inhibition of colon cancer proliferation and growth
Distribution of three proposed variants of UxaE-involving pathways for hexuronate utilization in Bacteria.A
Different linkage types of ubiquitin chains including Met 1-, Lys 11-, Lys 48-, and Lys 63-linked ubiquitin chains participate in the TNF-induced NF-Œ∫B signaling pathway and have roles in fine-tuning the regulation of the downstream cascade
The LUBAC complex participates not only in the TNFR complex I-mediated NF-Œ∫B signaling pathway, but also in the TNFR complex II-dependent apoptosis pathway
New targets in cancer cell metabolism are shown
Trans-interaction between cell type-specific CAMs, such as Duf (founder cell; with 5 Ig domains) and Sns (FCM; with 8 Ig domains), triggers distinct signaling events in founder cells and FCMs
Targeting the multistepped pathways of IL-1β–mediated inflammation
The Notch signaling pathway depicted between two cells in the neocortical germinal zone
Overview of the complement cascade and its regulators
A) Ischemia-Reperfusion Injury. Fo... B) APC & Alloreactive T cells. Cog... C) Antibody-mediated allograft inj... D) Chronic graft injury and fibros...
A comparison between the apoptotic pathways in C. elegans, Drosophila and mammals reveals conservation and expansion of the apoptotic pathway during evolution.
In different model organisms apoptosis and caspase activity have been observed to induce secretion of mitogenic factors, thereby promoting hyperplastic overgrowth or tissue regeneration
A. TNF ligation results in recruitment of RIPK1, TRADD, cIAP1 and cIAP2, and TRAF2 and TRAF5 to the TNFR1 to form complex I. cIAP1 and cIAP2 mediate Lys63-linked ubiquitylation of RIPK1, enabling docking of TAK1 (transforming-growth-factor-β-activated-kinase-1) and its binding partners TAB2 and TAB3.
This figure summarizes the mechanisms observed in blood cancers of hijacking the physiologic circuitry of their normal counterparts (left column) to drive tumor growth and manipulate endogenous immune responses (right column)
The extrinsic and intrinsic pathways of cell death may activate during adipocyte hypertrophy and result in adipocyte cell death
β-catenin may be activated and upregulated by a number of signaling components, and the canonical Wnt pathway serves as one of the most critical mechanisms for its expression
Radiation is known to induce the release of proinflammatory cytokines such as TNFŒ± by hematopoietic cells into the blood which could upregulate ATX production through NF-Œ∫B in the endothelial lining of blood vessels and other yet to be identified target cells
A schematic diagram depicting how peroxynitrite (ONOO-) is generated by iNOS and NADPH oxidase to stimulate [LMW-Fe]i response from a chelatable pool of iron for activation of IKK and NF-Œ∫B in LPS or TNFŒ±-treated macrophages
Proposed mechanism of CIB1 regulation of TNBC cell survival and potential role of CIB1 in non-oncogene addiction
Numerous arrestin functions play a role in apoptosis and cell survival
The hypothetical model illustrating p53 transgene mediated inhibition of Type I IFN signaling during VSV infection
The Ingenuity pathway analysis identified IFN pathway related transcripts that were differentially expressed in Suit2 cells
Apoptosis signaling pathways in cisplatin nephrotoxicity
Schematic model of regulation of PTPŒ± by STEP61 during EtOH treatment in DMS
A combinatorial approach to suppression of cancer growth that employs 4-HPR and tamoxifen
Model for brain signaling network reprogramming in response to mild mitochondrial uncoupling
Modulating effects of bioactive food components on niche signaling pathways and crosstalks among them in cancer stem cells
Vitamin D suppresses the β-catenin-dependent canonical Wnt pathway in both stem and non-stem colon cancer cells
The possible effects of soy isoflavone genistein and tea polyphenolic compound EGCG on the Wnt pathway in breast cancer stem cells
The proposed mechanism by which the HSP-peptide complex interacts with APC‚Äôs consists of cell surface receptor interaction
B cell-derived cytokines direct the ensuing immune response
The canonical Notch signalling pathway and relevant pharmacological inhibitors under development in cancer
The canonical HH-signalling pathway and pharmacological inhibitors targeting this pathway that are under ongoing development as anticancer therapies
The canonical Wnt signalling pathway and pharmacological inhibitors under investigation in cancer
Various growth factors activate PI-3kinase through their receptors, leading to activation of Akt ()
DENV interacts with target cells via one or more host factors that enhance attachment
ATR, activated by replication stress, and ATM, activated by the combination of replication stress and chromatin alterations, signal to downstream transducer and effector proteins
Schematic diagram of endogenous TRAIL function in multidrug-resistant cancer cells
Apoptotic signaling pathway induced by Licochalcone-A in head and neck squamous carcinoma FaDu cells
Antigen binding activates the BCR pathway through recruitment and activation of Lyn/Syk, which phosphorylates tyrosine residues on CD19, Nck and BCAP
Significant edges for the proteins in the PI3K-AKT kinase pathway for breast (a) and ovarian cancer cell lines (b) computed using a Bayesian FDR of 0.10.
Conserved and differential networks for the proteins in the PI3K-AKT kinase pathway between breast and ovarian cancer cell lines computed using a Bayesian FDR set to 0.10
The mitochondrial pathway of apoptosis is usually caused by disruption of mitochondrial membrane potential (ŒîŒ®m), release of cytochrome c, activation of caspase-9, and subsequent activation of downstream caspases-2, -3, -6, -7, -8 and -10, which eventually leads to apopto sis
FAS-ligand, TNF-Œ±, and TRAIL bind to their respective receptors leading to the recruitment of FADD via a death domain (DD) interaction
The detection of and response to external mechanical stimuli (i.e., compression, tension, shear, fluid shear stress) involves multiple pathways and signaling mediators including changes in intracellular calcium (Ca2+ ) through the release of intracellular Ca2+ stores or entry of extracellular Ca2+ through channels such as the store-operated, stretch-activated or mechanosensitive channels and voltage independent or dependent Ca2+ channels and the release of ATP and, at lower levels, UTP, following the activation of ionotropic P2X and metabotropic, G protein-coupled P2Y receptors in an autocrine/paracrine fashion
Cellular alterations and molecular mechanisms involved in hepatic cystogenesis
A combination of low oxygen tension and humoral mediators constrict the lung in-utero
Mechanical forces due to breathing, combined with increases in vascular flow and blood oxygenation act to dilate vessels of the lung
T-REX electrophile toolbox enables assessment of downstream signaling strength triggered by target-specific delivery of specific bioactive LDEs (1–10) to specific proteins in cells (e.g., Keap1) at a precise time
KEGG pathway analysis of proteins differentially phosphorylated by IL-33 using DAVID functional analysis tool indicated the enrichment of the Regulation of actin cytoskeleton pathway
The IL-17 receptor complex (IL-17RA/IL-17RC) is ubiquitously expressed and its ligands include IL-17A and IL-17F homodimers, as well as IL-17A/F heterodimers
The honey bee genome encodes major members of insect immune pathways including: RNAi (RNA interference); Jak/STAT (Janus kinase/Signal Transducer and Activator of Transcription); Toll; NF-κB (Nuclear Factor κB); JNK (c-Jun N-terminal kinase); and MAPK (Mitogen-Activated Protein Kinases), as well as orthologs of genes involved in autophagy, eicosanoid biosynthesis, endocytosis, and melanization
The extrinsic cell death pathway is typically triggered by members of the tumor necrosis factor (TNF) family of death receptor ligands, comprising TNF itself, Fas ligand, and TNF-related apoptosis-inducing ligand (TRAIL)
Signaling pathway of regulation of actin cytoskeleton
Summary of the potential mechanisms which may be involved in sustaining epithelial barrier function via the p-Akt signaling pathway
Model of CX3CL1-induced breast carcinogenesis in ErbB2 transgenic mice
The network is composed of two microenvironmental inputs (pro-growth indicated by white triangle and pro-death represented by black triangles), 7 internal nodes and two cell phenotypes (pro-growth and pro-death)
The inflammatory reflex controls innate immune responses by a mechanism that targets the regulatory transcription factor nuclear factor-Œ∫B (NF-Œ∫B)
In the cholinergic anti-inflammatory pathway, acetylcholine binding to nicotinic acetylcholine receptor subunit Œ±7 (Œ±7nAChR) leads to the inhibition of the phosphorylation of inhibitor of NF-Œ∫B (I Œ∫B), the downregulation of the activation of mitogen-activated protein kinases (MAPKs), inhibition of the release of intracellular Ca2+ stores and the formation of a heterodimeric protein complex with Janus kinase 1 (JAK2), which activates signal transducer and activator of transcription 2 (STAT3)
The mammalian base excision repair and single-strand break repair pathways
The PKD1/HDAC5/TFEB/MuRF1 axis mediates Ang II induced skeletal muscle atrophy
Overview of the proteostasis network (PN)
This cartoon summarizes our observations and integrates them into the context of previous studies
Differences in M1- versus M2-macrophage fueling reactions
The major components of the TGF-ß signaling pathway in normal fibroblasts
Neutralizing antibodies to αvß6 integrin block its catalytic activity, and inhibit latent TGF-ß activation only at sites where αvß6 integrin is expressed
The major mediator of tumor angiogenesis is vascular endothelial growth factor A (VEGF-A, also called VEGF), specifically the circulating isoforms of VEGF — VEGF121 and VEGF165
In mammals there are multiple deltalike ligands (Dlls), one of which, Dll4, is highly expressed in the vascular endothelial cells involved in angiogenesis
Roles of notch signaling in development and neurological disorders.The illustration depicts the canonical notch signaling pathway (center) and involvement in developmental processes (left) as well as adult neurological disorders (right)
Mammalian molecular clock and oscillation of mRNA and protein in peripheral tissues
Simplified schematic of the canonical Notch signaling pathway
An extracellular soluble cue binds to a multi-protein complex that is comprised of transmembrane receptor proteins and associated Janus kinases
IL-4RŒ± expression is regulated in the steady state by Hepatocyte growth factor-regulated tyrosine substrate (Hrs) (A)
Engagement of the type I IL-4 receptor by IL-4 brings about tyrosine phosphorylation of the associated JAKs, key tyrosine residues (pY1-5) in the cytoplasmic domain in IL-4Ra, STAT6 and IRS-2
Interferons and other inflammatory cytokines control HBV infection of hepatocytes via multiple, distinct mechanisms
Metabolic pathway for DEG based on previous animal studies and on the results presented in this report
Decreased fatty acid oxidation contributes to CKD progression
Simplified representation of the JNK signaling pathway in relation to the GR phosphorylation
Potential role of Lp(a) and PCSK9 in CAVD
Proposed pathways through which ethanol administration elicits alterations in cytokine gene expression
Arachidonic acid is released from cellular membrane phospholipids by phospholipase A2
Receptor activation (ligand binding) makes Ga to exchange GDP to GTP, Ga is then freed from the Gβ-Gγ dimer and activates adenyl cyclase (AC)
Schematic pathway of HIV-1 B and C differentially influence central nervous system
Proposed mechanism of XN in pancreatic cancer
Function of nuclear and cytoplasmic Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ)
Signal crosstalk with Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ)
A) Mesenchymal ste... B) Lamin-A,C level... C) On soft substra... D) By contrast, MS... E) High tension on... F) The contractili... G) On stiff substr...
The B cell receptor (BCR) signaling pathway and molecular interactions in the CLL microenvironment
A soluble recombinant molecule consisting of the extracellular domains of CD80 linked to the Fc domain of Ig (soluble CD80 or CD80-Fc) has the potential to maintain and facilitate T cell activation through three independent mechanisms
The diagram shows the proposed signaling pathway exerting the adverse effect of ET-1 on endothelium-dependent, nitric oxide-mediated vasodilation
(A) In the liver of obese humans and animal mod... (B) and macrophages (C) of obese animal models, the UPR is activate...
The HCV life cycle steps targeted by proteomic approaches are presented
This overview provides comparisons and contrasts between the current model and the emerging model
(I) FSH regulates induction... (II) Axin2 induction may su... (III) FSH binding to the G-... (IV) PKA also enhances the... (V) In addition, PKA regula...
The core inhibitory kinase module is composed of two groups of kinases, the mammalian STE20-like protein kinase 1 (MST1) and MST2, and the large tumour suppressor 1 (LATS1) and LATS2, in combination with their activating adaptor proteins, salvador family WW domain-containing protein 1 (SAV1), MOB kinase activator 1A (MOB1A) and MOB1B
Regulation of yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) activity goes well beyond the core kinases in the Hippo pathway
Yes-associated protein (YAP) can, in a context-dependent manner, function as a tumour suppressor by either inhibiting WNT signalling or triggering apoptosis
Transition of primordial to primary follicles
H2S-related pathomechanisms of diabetic endothelial dysfunction
PD-1 has both an intracellular immunoreceptor tyrosine-based switch motif (ITSM) and immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail
PD-1 and its ligands are regulated by a complex network of factors
The canonical Wnt/β-catenin pathway antagonizes the β-catenin destruction complex, consisting of Axin, GSK3 and APC to promote target gene transcription
The Wnt/PCP pathway modulates actomyosin dynamics and vesicular trafficking to control mediolateral and radial cell intercalations, apical constriction, collective and individual cell migration and oriented cell division
Proposed mechanisms of activation of proinflammatory signaling pathways in IFN-mediated autoinflammatory diseases
Potential mechanisms of NF-Œ∫B-mediated diseases
Spearman rank correlations between cytokines significantly modified by age (see ; p-values < 0.0001 according to a Bonferroni-Holm correction) were plotted to reveal signaling networks.
(a) ERŒ± binds to estrogen and gets activated in the cytoplasm. After ac... (b) The non-genomic action of ERŒ± occurs transiently outside the nucleu...
Overview of the key transduction molecules of ErbB signaling pathway known to regulate cardiomyocyte viability and function
a | Inactivation of E2F-dependent cell cycle transcription involves multiple negative feedback mechanisms
A, Death ligands activate opposing signals leading to apoptosis via a caspase pathway, or to alternative pathways via kinases and NF-Œ∫B
Arachidonic acid metabolites are critical mediators of host defense against Mtb
CXCR3 Isoforms play functional roles in seemingly opposing directions
Differential effects of Calmodulin on two key K-Ras4B effector pathways
Classical (genomic) and non-classical (non-genomic) mechanisms of E2 action
Emerging concepts in the regulation of hematopoiesis by inflammatory signaling
Pictorial depiction of the key proteins affected via altered transcription and translation by the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat
Arachidonic acid (AA) is metabolized to 20-HETE by cytochrome P450 (CYP) œâ-hydroxylases of the CYP4A/CYP4F subfamilies
An outline of the inhibition of type I IFN signaling pathways by viral proteins of KSHV
A complex crosstalk exists between the energy-sensing pathways in mammals
(1) First, ligands bind to receptors to promote receptor phosphorylation
(A) In a normal glioma cell with an intact PI3K pathway, T cells are abl... (B) In a glioma cell with aberrant PI3K pathway signaling, PD-L1 express...
Cross-regulation of GPCR and Nox signaling pathways can induce cell death by apoptosis
Proposed signaling pathway based on data presented in this article
. Proposed model of how S100P/RAGE signaling can promote colorectal cancer progression by linking inflammation to RECK down-regulation via the induction of miR-21.
Binding of hepatocyte growth factor (HGF) to c-MET, homodimerization, and autophosphorylation (denoted by orange circles containing “P”) elicit downstream signaling mediated by adaptor proteins (Gab1 and Grb2) to induce activation of the phosphotidylinositol-3 kinase (PI3K), Ras/Raf/MEK/ERK, and the Cdc42/Rac1 pathways
Involvement of IAP proteins and IAP antagonists in the apoptosis and NF-Œ∫B pathways [, ]
Antiviral activities of Dicers(A) Domain architectures of Dicers from Drosophila melanogaster and Caenorhabditis elegans, and human
RecQ helicases in base excision repair (BER) and double-strand break repair (DSBR)
SIRT1 functions as an intracellular energy sensor to detect the concentration of NAD+, and regulates metabolic status by deacetylating various target proteins including transcription factors such as FOXO3 and PGC-1α
The immunosuppressive and tumor-promoting functions of TAMs and MDSCs in HCC
A schematic view of bench-to-bedside aspects of colorectal cancer epigenetics
(A) Schematic of the ERBB(EGFR)/KRAS/BRAF/MAPK signaling axis, and its c... (B) COX and 15-PGDH reciprocal relationship. In sporadic CRCs, Cox-2 is...
Overview of putative pathways of catecholamine autotoxicity in a dopaminergic neuron
A model of metabolic inflexibility in beta cells
Altered modulation of the IL-8 signaling pathway in AH livers with MDBs
The signaling pathways of VEGF and HER family members and the current drugs that target these proteins in cancer are shown
Endoplasmic reticulum stress inducing autophagy
Schematic model of the involvement of LRP6 in the PTH-stimulated anabolic bone effect
Myc-regulated metabolic pathways in cancer
Schematic representation of the IGF-1R signaling network and nodes of therapeutic blockade
Cellular interactions in normal and diseased vasculature
Viruses can be detected by one of four classes of pathogen recognition receptors in cytoplasm or endosome of CNS cells: TLRs (e.g., TLR3 and TLR7), RLRs (e.g., RIG-I and MDA5), NLRs (e.g., NLRP3), or DNA sensors (e.g., cGAS).
Cancer-promoting GSNs in A) D-SWCNT, B) D-MWCNT and C) ASB neoplastic-like transformed SAECs
Glutamate binds to NMDARs, leading to Ca2+ influx and PKA phosphorylation, which in turn, directly and indirectly through ERK1/2, activates CREB
A. Canonical signaling pathways are typically defined as those that are dependent on the stabilization of the β-catenin protein.
The IGF1R is comprised of two α and 2 β subunits
(A) CDC42 signaling pathways that regulate the... (B) Subjects with schizophrenia exhibit up- or... (C) Predicted functional consequences in schizo...
(A) Host and virus control of imme... (B) Protein complexes involved in... (C) Viral modulation of cellular s... (D) Control of cell cycle progress...
Lipidomic view of phospholipase A2 (PLA2), cyclooxygenase-1 and -2 (COX1/2), 5-lipoxygenase (5-LOX), 8-, 12-, and 15-lipoxygenases (8/12/15-LOX) and cytochrome P450 epoxyhydrolase (CYP) pathways of eicosanoid biosynthesis derived from arachidonic acid
TLR4-mediated priming of macrophages by LPS induces pro-IL-1β production via activation of NF-Œ∫B
Proteins in the tight junction signaling pathway as determined by Ingenuity Pathway Analysis (IPA) software
In plants, effector-triggered PCD is initiated by NB-LRR-mediated perception of the presence of specific intracellular effectors secreted by pathogens
Systematic identification of signaling pathways conferring functional resistance to drugs
Genes that drive growth or cancer progression are shown in green
A simplified model of a cell signaling process highlighting the flow from signals generated externally by epidermal growth factor (EGF) to the activation or repression of transcription
Bile acids, after synthesis, are secreted into the bile where bile acids, cholesterol and phospholipids form micelles
Summary of unfolded protein response and endoplasmic reticulum stress signaling pathways
A model depicting Dcp1-mediated translational repression in endotoxin-tolerant cells
RTK: receptor tyrosine kinase; EGFR: epidermal growth factor receptor; AR: androgen receptor
The mTOR pathway as a central signaling pathway causing malformations of cortical development and epilepsy
A large contributing factor to cancer cachexia is the presence of inflammatory cytokines such as TNF-Œ± which act to both suppress appetite and stimulate the proteasomal degredation pathway through activation of NF-Œ∫B
Upon binding to graft microvascular endothelial cells (EC), leukocytes, inflammatory cytokines, growth factors (incl
Inflammatory bowel disease (IBD) as a multifactorial disorder
Modeling the calcium-mediated pro-apoptotic action of less toxic natural products
Model for the Ca2+ dependent signaling pathway activated by PAR2
Regulatory mechanisms of ectodomain shedding
The protective signals of limb IPC may be transmitted to remote target organs like the kidney via different communication mechanisms, including humoral mediators, neurogenic pathways, and systemic regulation of immune-competent cells
Signaling pathways induced following CB2 engagement with cannabinoid ligands
Comparison of typical innate immune signaling cascades (top panel) with those activated by CJD infection (bottom panel)
Model of signal transduction pathway for delayed onset potentiation of the NMDA response by PregS
Nuclear and cytosolic pathways controlling nuclear Ca2+ homeostasis in cardiomyocytes
An integrated view of receptor-initiated nuclear Ca2+ signals in cardiomyocyte
The schematic pathways shown in the figure are derived from the findings of multiple studies described in the main text
The major mechanisms of IL-27-induced suppression of arthritic inflammation shown in the figure are derived from multiple studies described in the main text
Regulation of the JAK-STAT signaling pathway
TLR and NF-Œ∫B signaling disrupted by PID
A diagram of Hh signaling in mammalian cells
Different roles of Hh signaling in cancer
Activity-dependent NMDA signaling induces the CREB signaling pathway, which upregulates the expression of miR-132 and BDNF
Stalling of replication forks on DNA ICLs induces lesion recognition by the FANCM–FAAP24–MHF1/2 complex and subsequent recruitment of the FA core complex, which in turn recruits the mono-ubiquitinated FANCD2-FANCI to the ICL region
Model for APOBEC3B upreglation by the PKC-NFŒ∫B pathway.PKCŒ± activation by DAG or PMA leads to IKKŒ± phosphorylation and proteasome-dependent cleavage of NFŒ∫B subunit p100 into the transcriptionally active p52 form
A) Proposed response of CTCL cells with downregulated/absent expression... B) Proposed response of CTCL cells to ePDT. The binding of fully functio...
ERBB signaling pathway is highly activated in AA PCa specimens
Ibrutinib targets BTK, a kinase that is critical for signal transduction through the B-cell receptor pathway.BTK: Bruton’s tyrosine kinase; CLL: Chronic lymphocytic leukemia.
GRP-78/BiP chaperone protein represents one of the key molecules targeted by MDA-7/IL-24
Schematic diagram showing the convergence of WNT and NOTCH signaling onto cell cycle regulation
Molecular regulation of osteoclast survival: In WT osteoclast, both RANK and Ras-Raf-1-MEK-ERK signaling contribute to cell survival, but survival is mainly regulated by Src-Cbl-PI3K pathway
mTORC2 signaling controls metabolic reprogramming in GBM: mTORC2 reprograms the glycolytic metabolism, lipid, glutamine, nucleotide and ROS metabolism mainly through Akt and c-Myc
This figure shows how the microenvironment can transform the phenotype of MDSCs into pro-tumor cells
M1 macrophages appear to promote carcinogenesis in the bladder
Activation of the complement cascade and its role in tumorigenesis
Cartoon diagram of the hypothesized effects of mechanical loading, with or without LVAD support, on cardiac 7-TMR/GPCR signal transduction
The choice between C-NHEJ, MMEJ and HR is regulated by multiple factors and influenced by the cell cycle
Consumption of a high-fat diet (HFD) increases TOR signaling, leading to decreased ATGL/Bmm-PGC-1/srl and increased SREBP-FAS functions
Inhibition of YAP/TAZ transcriptional coactivators by LATS1/2
Regulation of the Hippo pathway in Drosophila
Regulation of the Hippo pathway in mammals
Therapeutic targeting of the Hippo pathway
Highlighted nodes represent genes from all heatmaps in – that were differentially expressed between myxomatous and non-myxomatous valves
Scopolamine blockade of Ach-M1 receptors located on GABAergic interneurons results in disinhibition and a burst of glutamate transmission, activation of AMPA receptors, and depolarization of postsynaptic pyramidal neurons
PDEs 1–4 (orange symbols) hydrolyze cAMP (yellow shaded background) generated by the β-adrenergic signaling pathway (red shaded background)
A paradigm for testing the multiple independent mechanisms that reinforce IDO1-mediated immunosuppression in malignant glioma
Specific mRNAs are inefficiently translated (repressed) in undifferentiated germ cells
A) In the presence of wild-type merlin, mutant RAS modestly increases MAPK signaling, which is insufficient to drive tumorigenesis ()
Overview of the signaling pathways associated with CRKL, GAB2, and FRS2.CRKL is activated by multiple types of cell surface receptors including integrin receptors upon binding to extracellular matrix (ECM), cytokine receptors, and growth factor receptors
Proposed signaling mechanisms of S100A8/A9 in pancreatic-cancer cells.S100A8/A9 could interact with RAGE, leading to the activation of MAP kinases and NFÃÉŒ∫B signaling
Signaling of S100A2, S100A4 and S100A6 in pancreatic-cancer cellsIn pancreatic cancer, the expression of S100A2, S100A4 and S100A6 has been shown to be regulated by the transcription factor, GLi1, an important downstream element of the sonic hedgehog pathway that has been implicated in pancreatic ductal adenocarcinoma
(A) Organisation of the proteins involved in the primary (proximal) and... (B) Supersaturated proteins (in red) in the KEGG `Alzheimer's disease pa...
Signaling schematic depicting our hypothesis of how adenosine regulates HCASMC cell-cycle progression
Hippo signaling pathway and main regulators
Proposed pathway of prostaglandin synthesis and interaction with the cyclooxygenase pathways and VEGFA
The transcriptional activity of YAP may be induced by NRG1- and proteolysis-mediated activation of ERBB4 signaling
The mevalonate pathway, NHRs and immunity
IL4 induces heterodimerization of the IL4RŒ± and γC subunits to form the type I IL4 receptor in hematopoietic cells including lymphocytes (depicted)
Three major signaling pathways that regulate cell size in normal cells.A
A G protein-coupled receptor initiates a signaling cascade upon activation at the cell surface
The normal homeostatic regulation of the hypothalamic-pituitary pathways due to stimulatory (+) and inhibitory (−) signals is shown
Schematic of a subset of the Hippo pathway with known roles in the liver
Colored shapes represent the known effectors of the Hippo pathway that, when knocked out or overexpressed, are associated with the development of the indicated form of cancer
Endothelial cells are connected with each other through the tight junction (TJ), adherens junction (AJ) and gap junction (GJ) proteins
Every major signaling pathway that is activated in a contracting muscle fiber during and after endurance training converges on PGC-1α by modulating PGC-1α gene expression and/or post-translational modifications of the PGC-1α protein
TGF-β-activated non-Smad pathways in epithelial-mesenchymal transition
Smad complexes can cooperate with transcription pathways in the control of gene expression in epithelial-mesenchymal transition
The architecture and signaling of the Drosophila testis niche
Molecular pathogenesis and potential treatments for thrombotic microangiopathy in the glomerular endothelium
Complexity of the direct and indirect effects of mTOR on signaling pathways
Proteins implicated in Parkinson’s disease (PD) maintain a healthy pool of mitochondria
Extrinsic apoptotic pathway is induced by activation of the membrane death receptors that leads to activation of the effector caspases and triggers caspase cascade that leads to cleavage of the caspases final targets, among the others: nuclear lamins, DFF45, PARP
Activation of TNF receptor leads to activation of RIP1 and RIP3 kinases when caspase-8 is not present or inactive
Proposed opposing modulation of the AMPK pathway for energy homeostasis by utilizing the AMPK pathway
Activation of protein synthesis downstream of MYC supports tumor progression
Model for the integration of the DUOX2 system into the intestinal epithelial defense response
TNF-Œ± can bind with either of its receptors and initiate several pathways: activation of NFŒ∫B dependent signaling can lead to beneficial effects [, ]
If ER stress is irremediable, IRE1α becomes hyperactivated and undergoes homo-oligomerization
Mechanisms of TLR4 and TLR3 sensitization
AMPK activation phosphorylates TSCs at Ser 1227 and 1345 leading to the inhibition of mTORC1
A schematic representation of the Ras signaling pathway
NRG1 activates ERBB4 and induces proteolytic cleavage and release of membrane- anchored and soluble forms of the ICD
Schematic of described mechanisms involved in steroid hormone regulation of cancer stem cell populations
Schematic diagram shows major signaling pathways stimulated by IFN-Œ±/β (mediated by the type I IFN receptor) and viral pathogen-associated molecular patterns (PAMPs) and/or ICs-containing nucleic acids (mediated by endosomal TLRs)
Schematic representation of complete oxidation of glutamate via the ”pyruvate recycling pathway” (essential enzymes in red) and de novo synthesis of glutamate and glutamine from glucose via pyruvate carboxylase (PC) (essential enzymes in blue) in astrocytes.For de novo synthesis of glutamate and glutamine, glucose is metabolized to acetyl CoA and oxaloacetate via pyruvate dehydrogenase and pyruvate carboxylase, respectively
[U-13C]Glutamate (GLU) may be completely metabolized to CO2 via the “pyruvate recycling pathway”
The MAPK pathway has been invoked in phospholipase A2 activity that could release arachidonic acid, perhaps in concert with VEGF, and thereby amplify 20-HETE formation ()
Cellular dormancy is governed by a combination of external and internal cues
Targeting BCR signaling attenuates homing, survival, EMDR and MRD of malignant B cells
The virus engages the internalizing receptor Coxsackie-Adeno Receptor (CAR) whose tyrosine kinases Fyn and Abl can facilitate viral remodeling of cytoskeleton to gain entry, further aided by co-receptor decay accelerating factor (DAF), associated with tyrosine kinase p56lck
The main signaling pathways of viral DNA sensors are depicted
Simplified outline of Insulin and AA/TOR signaling pathways
ABL kinases are activated downstream of hyperactive receptor tyrosine kinases (RTKs), chemokine receptors and SRC family kinases, or in response to oxidative and metabolic stress pathways
Ingenuity Pathway Analysis of the subset of day-one genes that differentiate long-term success or failure, divided into two groups (F and G) following an unsupervised cluster analysis
A) The classical pathway of complement is activated when C1q binds to Ig... B) Complete complement activation generates several biologically active...
miRNA targeting of insulin signaling occurs centrally at the beta cell and peripherally in target tissues
The Figure depicts the major metabolic pathways activated during fasting and transcription factors involved in each of them
Proposed pathway for the metabolism of efavirenz to a nephrotoxic metabolite(s), which is believed to result from activation of the cysteine conjugate, either through S-oxidation
(A) The complement response as a driver of clin... (B) A molecular view of C3 activation and its r... (C) The various concepts to therapeutically con...
(A) In this model the activation of the heterot... (B) In this model the activation of G-proteins... (C) In analogy with electronic circuits, the si...
A and B, top two networks of proteins eliciting a significantly elevated (P < 0.01; mean ratio > 2) response in C3(1)-T TNBC mouse model samples collected before palpable tumor compared with baseline, based on Ingenuity Pathway Analysis.
Shown are the glycolytic pathway and the mitochondrial TCA cycle
Metabolic reprogramming of the inflammatory (LPS/IFNγ activated) macrophage involves increased expression of HIF1 and PKM2 protein, which increases glycolysis
Cell-intrinsic versus cell-extrinsic control of metastatic progression by miRNAs
Engagement of the TCR as well as the iVŒ±14TCR leads to activation of PLCγ1, which hydrolyzes membrane bound PIP2 into membrane bound DAG and soluble IP3
mTOR signals through two functionally distinct complexes: mTORC1 and mTORC2
TLRs signal through MyD88-dependent and MyD88-independent pathways.1) MyD88 signaling pathway.
Representation of the possible connections between transcriptional programs, metabolism, epigenetics, and T cell differentiation states
(A) APN regulates a SDF-1 chemotactic gradient for BMSCs migration from the bone marrow to the circulation by increasing SDF-1 concentration in circulation and decreasing SDF-1 expression in bone marrow after injury
In response to tissue damage, damage-associated molecular patterns (DAMPs) molecules including alarmins such as HMGB1 (high-mobility group protein B1) and HSPs (heat shock proteins) bind to and activate the TLR4 receptor (toll-like receptor 4) on the surface of innate immune cells
The high expression of active IDO1 leads to a commensurately high rate of tryptophan conversion and depletion
Oxidative stress induces ABC efflux transporter expression
Gc can interact with various immune cells to elicit innate inflammatory responses and suppress Th1/Th2-mediated specific immune responses
Integration of Akt and mTORC1 signaling into the IL-4R and TLR4 pathways
Simplified scheme of sulfur metabolism with an emphasis on the H2S-generating reactions
The mitochondrial sulfide oxidation pathway
Cytokine signaling and activation of TNFR and TLR is propagated through adaptor molecules such as TRADD, TRAFF, IRAK and MyD88 leading to phosphorylation and activation of the IKK kinase complex
(A) Direct and indirect interactio... (B) Representative pSer473 AKT and... (C) Representative LC3 Western blo... (D) Quantitative analysis of autop...
(a–k) 11 genes were significantly overexpressed during influenza infection in all discovery cohorts analyzed
(A) Venn diagram showing the number of expressed genes (FPKM > 0.5 in 10... (B) Venn diagram showing the number of GO terms derived from the high gr...
Apoptotic cell engulfment via integrins, BAI1 and CED-1 homologs utilize Rac1 to facilitate actin re-arrangement
Within B cells, dendritic cells, and macrophages, the engagement of TLR7 with ligands, hY3 and Alu RNA, in the context of the two-receptor hypothesis (not shown) results in activation of pathways driven by epigenetic modifications influencing the transcription factors STAT1 and NF-Œ∫B
A) KRAS promotes glucose metabolism in PDA cell... B) In addition, PDA cells have enhanced activit... C) KRAS also activates and reprograms glutamine...
Pattern recognition receptors, including Toll-like receptors, RIG-I-like receptors and DNA receptors, interact with their cognate adaptors and activate the canonical IKKŒ±βγ complex
In response to viral infection, pattern recognition receptors activate the NF-Œ∫B pathway, while viruses target key signaling components to modulate NF-Œ∫B activation
Normally, stimulation of cell surface receptors, including NMDA receptors (NMDARs) and group 1 metabotropic glutamate receptors (mGluRs; such as mGluR5), results in the activation of the phosphoinositide 3-kinase (PI3K),, mammalian target of rapamycin complex 1 (mTORC1; which comprises mTOR bound to regulatory-associated protein of mTOR (RAPTOR)) and extracellular signal-regulated kinase (ERK)signalling pathways in neurons
The Wnt canonical and non-canonical pathways
Mechanisms of resistance to androgen deprivation therapy demonstrating AR ligand-dependent and ligand-independent mechanisms.AR: Androgen receptor; AR-V7: Alternate splice variant 7 of the androgen receptor (it is unknown currently if HSP bind to the AR splice variants); DHT: Dihydrotestosterone; HSP: Heat-shock protein; P: Phosphorylation; RTK: Receptor tyrosine kinase; S: Other steroids (e.g., glucocorticoids).
Pathways of contraction and relaxation in cavernosal smooth-muscle cells
Reviews of Wnt-mediated cellular responses that do not utilize β-catenin can be found in [, ]
Left: Inhibition of endoplasmic reticulum-localized Porcn results in loss of Wnt fatty acylation
The known input signals are indicated at the top of each pathway (at the level of the plasma membrane) and the key identified components of the pathways are shown below as ovals
Schematic diagram showing the inhibitory effects of triptolide on oxaliplatin induced upregulation of nucleotide excision repair pathway
Our current work demonstrates that direct activation of Epacs in sensory neurons with the Epac-selective cAMP analogue, 8CPT-AM, subsequently activates Rap1 and Ras small GTPase proteins
Working model illustrating the putative regulatory pathway in pancreatic cancer stem cells that is stimulated by nicotine and inhibited by GABA
(A) Upon entry into the mammalian hosts, Leishmania parasites first come... (B) TLR2 and TLR4 on macrophage recognize Leishmania outside, whereas TL...
Key signaling pathways involved in minocycline-mediated protection of cardiac myocytes from apoptosis trigged by in utero cocaine exposure
A schematic depiction of the pathway for CaMK-dependent signaling
Inhibitors of the UPS targeting proteins involved in the intracellular circuits of carcinogenesis.FAF1 = Fas associated factor 1; SCF = Skp-Cullin-F-box, FBXW7 = F-box and WD repeat domain containing 7, p27Kip1 = cyclin-dependent kinase inhibitor 1B, c-Myc = Myc proto-oncogene protein, USP = ubiquitin-specific-processing protease, HAUSP = herpesvirus-associated ubiquitin-specific protease, Hdm2 = human double minute 2 homolog, p53 = tumor suppressor p53, Mcl-1 = induced myeloid leukemia cell differentiation protein, AP = apoptosis protein, XIAP = X-linked inhibitor of apoptosis protein, cIAP = cellular inhibitor of apoptosis protein, NF-Œ∫B = nuclear factor Œ∫B; IŒ∫B = inhibitor of nuclear factor Œ∫B, DUB = de-ubiquitinase, BRCA1 = breast cancer 1, early onset, HIF1Œ± = hypoxia-inducible factor 1-alpha, FANC = Fanconi anemia (FA) pathway, VHL = von Hippel Lindau tumor suppressor, RAD6 = ubiquitin-conjugating enzyme E2 B
MyD88-dependent TLR signaling can be inhibited at any step along the signaling pathway
Signaling through TREM2/DAP12 inhibits TLR responses through the DAP12 ITAM tyrosines, Syk and Btk/Tec
(A) IL-33 is released by secretion from stressed cells (17,18 (B) non-self molecule (i.e. bacteria or alloantigen [, ], IL-33 drives a...
Pathophysiology of Cardiac Toxicity from Various Chemotherapeutics and Role of Preventative Therapies
The calcineurin-NFAT pathway: Activation and regulation
Promotion of cancer development and progression by NFAT
Inhibition of the calcineurin-NFAT pathway at multiple levels
Wnt signaling in old HSCs switches from a canonical β-catenin-dependent pathway to a non-canonical pathway associated mainly to Wnt5a []
Signaling pathways of cytokines in GnRH neurons
A. The estrogen receptor-dominated cell growth in estrogen-dependent cells.
Top biological network generated by Ingenuity Pathway Analysis for differentially expressed proteins of (A) ALDH+/CD44+CD24−, (B) ALDH+/CD49f-EpCAM+ and (C) CD44+CD24−/CD49f-EpCAM+
After translation, nascent HIF-1Œ± interacts with the molecule chaperone Hsp70/Hsp90 system for processing and maturation
BCR triggering by an antigen induces activation of early kinases, including LYN and SYK [], which then transduce the signal to cytoskeletal activators, including HS1 protein [, ], and to other early effectors of the signaling response, including BTK kinase []
Phosphorylated tyrosine residues in exon 13 (Y663) and exon 14 (Y686) serve as binding site for SHP-2 phosphatase [], and bound SHP-2 attenuates EC migration by inhibition of MAPK/ERKs signaling pathway []
TGFβ bound TGFβRII recruits TGFβRI (ALK5 or ALK1), forms a heteromeric complex, and phosphorylates TGFβRI
(A) Diagram of how the MAPK pathwa... (B) Pol I transcription can be reg... (C) eIF4F complex inhibition. mTOR... (D) Ternary complex inhibition. Ac...
(A) Pathway of hyperglycemia-induction of intrarenal RAS activation and... (B) Antagonistic effect of exogenous Ang 1-7 on intrarenal RAS activatio...
The novel promising anti-inflammatory therapies
(A) In the simplified pathway representation, heterogeneous nodes and ed... (B) In the network representation, all nodes correspond to the same type...
In cancer cells an increased uptake of glucose occurs as well as diversion of glycolytic intermediates to biosynthetic pathways including nucleosides, amino acids and lipids, which support cell growth and proliferation
(A) In ER-negative breast cancer cells, EZH2 ac... (B) In ER-positive breast cancer cells, EZH2 ph... (C) In castration-resistant prostate cancer (CR...
(A) The PRC1 subunit, BMI1, acts as an activator of the WNT pathway by r... (B) The binding of TNFŒ± to the TNF receptor (TNFR), causes the recruitm...
Signaling crosstalk between the TGF-β-activated Smad pathway and the Wnt- and Notch-activated signaling pathways during EMT
Schematic representation of the canonical NFŒ∫B signaling pathway
ConTour shows a multitude of heterogeneous data items in several columns in the relationship view (bottom)
(a) DDN, (b) GDNMES, and (c) GDNnon-MES of Integrin Œ±IIb β3 signaling (M760) pathway
(a) DDN, (b) GDNPN, and (c) GDNnon-PN of PI3K events in ERBB2 signaling (M570) pathway
Network of genes located within high-level copy number changes and deregulated across all of the cell lines and tumors
The key signaling pathways that regulate activity-dependent translation initiation in neurons
Shown is a summary of core, conserved molecular processes in SSc skin
Because KAT2B is a novel genetic susceptibility factor for drug abuse, we built a GeneMANIA () network centered around KAT2B to find related genes that may have functional links to drug abuse
Schematic representation of BMP signal transduction
Dotted lines denote tumor suppressors and solid lines denote activated or over produced proteins that contribute to tumor development
(A) The centrosome cycle is entrained with the... (B) Activation of the DNA damage response pathw... (C) Centrosome dysfunction can itself alter cel...
MST1/2 kinases, in complex with the scaffolding protein SAV1, directly phosphorylate LATS1/2 and MOB1
Multiple cellular stressors modulate the expression levels of pro- and anti-apoptotic BCL-2 family proteins (red and green respectively), leading to the activation of BAX and/or BAK and mitochondrial depolarization
Examples of commonly occuring cancers driven by specific oncogenic driver mutations that result in constitutively activated downstream kinase signaing pathways and suppression of the mitochondrial apoptotic pathway
Key components of the PI3K/Akt signaling pathway examined in the GalT-deficient mice are depicted in green squares
MDM phagosome network identified in (A) HIV-1-infected and (B) HIV-1-infected with URMC-099 and nanoATV treated cells
Metabolism and the circadian clock converge
HDM and IL-17A activate p38 MAPK signaling in airway epithelial cells (AEC) to induce TNFŒ± converting enzyme (TACE) or another member of the a disintegrin and metalloproteinases (ADAM) family to cleave EGFR ligands such as amphiregulin (AREG), on adjacent cells or on its own cell surface, that activate EGFR signaling, which drives the production of GM-CSF
(A) TCR engagement initiates PD-1 transcription through NFATc1 binding a... (B) In B cells, the recruitment of SHP-2 reduces the tyrosine phosphoryl...
In the cellular immune response, IFN-γ serves as a measure of T-cell activation
A (a) PD-1 is highly expressed on naïve B cells. In T cell–independent hu... (b) In sharp contrast with the innate-like response, PD-1 signaling act...
Tumor cells typically overexpress PD-L1 due to intrinsic factors (genetic alterations, activation of certain signaling pathways, and viral infection) and extrinsic factors (cytokines, such as IFN-γ, secreted by T cells attempting to destroy tumor cells)
The primary pathway through which class I PI3K activates mTORC1
Network mapping of genes with >5-fold expression change using IPA
Components of cytokine signalling pathways and associated transcriptional responses affected in PIDs and detected as genetic risk loci for common inflammatory diseases (red lettering)
(A) TGF-β1 regulates collagen synthesis and accumulation to maintain homeostasis under physiological conditions
Under this model, when tissue O2 levels fall, O2 is released from haemoglobin contained within circulating erythrocytes
Exposure of human erythrocytes to PGI2 or its analogs results in activation of the heterotrimeric G protein, Gs
Connectivity of differentially expressed genes in the important signaling pathway following mixed PCBs exposure in human PBMC in vitro depicting the connectivity between genes expressed (with ‚â•1.5 fold change, t-test, p <0.05)
PSME3 regulates host defense against bacterial pathogens by regulating the stability of the transcription factor KLF2
Working model of an integrated axon degeneration signaling cascade
Levels of PDZ-RhoGEF, an activator of the RhoA small GTPase, decrease in the cytoplasm and increase in the nucleus of NAc MSNs 24 hr after the last chronic cocaine dose
Second generation RAF inhibitors such as vemurafenib and dabrafenib are BRAF-selective and cause paradoxical activation of ERK (panel (a))
A, Schematic representation of Wnt signaling cascade and cadherin-based mechanical interactions between adjacent cells
Key components searched for in five investigated immune related pathways
Pathways involved in internalization and sensing of dsDNA
Simplified representation of the extracellular signal-regulated kinases (ERK)1/2 branch of the mitogen-activated protein kinase (MAPK) signaling pathway and its interaction with xanthine oxidoreductase (XOR) and nitric oxide (NO)
Growth factor binding to receptor tyrosine kinases (RTKs) activates downstream signaling through the PI3 kinase and MAP kinase signaling pathways
The biosynthetic pathway of mycolyl arabinogalactan
Overview of the PI3K/AKT/mTOR pathway and cellular processes controlled by downstream signaling
A model summarizing the epigenetically regulated MLL2/FOXO/BRD4/c-Myc- axis in reducing the sensitivity of the HER2+ breast cancer cells to Lapatinib, and the synergy of Lapatinib and IBET in suppressing HER2+ breast cancer
(A) Network of osteogenic specific proteins regulated by BMP2 signaling. (B) RT-qPCR generated profile for the normalized expression of genes aft...
(A) Merlin isoform I has three structural regions: a tri-lobed aminoterm... (B) Active state of merlin. In this state, merlin mediates its tumour su...
Schematic representation of cytokine-mediated cascade associated with chemotherapy-induced cognitive dysfunction
Regulation of enterohepatic circulation of bile acids by FXR
Membrane-bound TNF (mTNF) is processed by the metalloproteinase TACE/ADAM-17 to the soluble form (sTNF)
The PI3K/AKT/mTOR signaling pathway and a proposed model for its regulation through the evaluated miRNAs
Olfactory receptor (OR) signaling pathways
RNA was extracted from skin wounds and in epiVDRKO and littermate control mice 3 days post wounding
Proposed mechanism by which activation of BDNF receptor TrkB using 7,8-dihydroxyflavone (7,8-DHF), a small-molecule TrkB agonist, improves brain plasticity and mental health following traumatic brain injury (TBI)
Schematic of different PRRs in the cell and the signaling pathways that are activated by each PRR
IRF6 regulates the switch between proliferation and differentiation, and loss of function mutations lead to orofacial clefting
A. Under normoxic conditions Ewing sarcoma cells constitutively express NPY and its Y1R and Y5R.
miR-27 fine tunes osteoblast differentiation by positively regulating canonical Wnt signaling and negatively regulating Runx2 activity
An overview of the regulation of transcription by YAP/TAZ transcriptional co-factors and the regulation of YAP/TAZ activity in mammalian cells
Interconnections between the Hippo and RB/E2F pathways
Potential signaling pathway alterations in Kupffer cells after alcohol and/or burn injury
p38 pathways regulate Ras oncogene activity by negative feedback (A) and signaling integration (B)
The AIM2 inflammasome is activated by a number of microbial pathogens and dsDNA ligands, including the DNA virus mouse cytomegalovirus (MCMV), the cytosolic bacterium Francisella novicida and the dsDNA ligand poly(dA:dT)
Model for the mechanism of Wnt-mediated suppression of osteoclast differentiation
The schematic shows the organization of the RAS-ERK pathway
Muscle wasting processes are regulated by a number of receptor mediated signaling pathways
Multiple pathways converge on the myofibroblast phenotype
(A) The cN cross-talk signaling network model is composed of the β-adrenergic pathway (red background), the NO/cGMP/PKG signaling pathway (blue background), and cross-talk between them (yellow background)
(a) In neural progenitors, agonist binding to cannabinoid receptors couples to the PI3K/Akt/mTORC1 pathway via Gi proteins
Molecular mechanisms of ethanol-associated OESCC
Schematic diagram of the polyp to colorectal cancer sequences
Diagram of the role of RKIP in various signaling pathways
Mosquitoes ingest an arboviral-infected blood meal into the midgut
The intrinsic cell death pathway is initiated by an intracellular death signal
Three mechanisms and related signaling that underlie Tat-mediated increases in Ca2+ influx/[Ca2+]in and hyper-excitation of mPFC pyramidal neurons
NSAIDs inhibit PGE2-induced tumorigenesis through targeting multiple downstream signaling pathways of PGE2
A) Schematic summarizing our and o... B) Schematic summarizing our work... C) Schematic summarizing our and o... D) Schematic summary of plausible...
Sperm contact with the egg jelly triggers production of NAADP (1), which has been implicated in vesicle membrane fusion for the acrosomal reaction (2) and/or suggested to be delivered as the activating molecule to the eggs
Insulin crosses the blood brain barrier (BBB) via a carrier facilitated process to activate insulin receptors in the CNS and stimulate similar signaling cascades as has been described in peripheral tissues such as skeletal muscle and adipose tissue
The expression of Sox2 and Nkx2.1 are regulated by a complex set of mesenchymal (blue) and endodermal (dorsal marked by pink and ventral marked by green) signaling events involving BMP, Eph-ephrin, FGF and WNT signaling.
A) Arrestins extend the GPCR signaling pathway beyond G proteins by scaf... B) Arrestins regulate protein spatiotemporal distribution. GPCR stimulat...
Cardiac-specific pathways were examined for enrichment in differentially methylated genes using Ingenuity Pathway Analytics, revealing cardiac development to be physiological process most targeted by differential methylation after ISO
Schematic diagram of a proposed model illustrating how SOX4 interacts with PI3K-AKT, Wnt-β-catenin, and AR signaling pathways, and how the PI3K-AKT-mTOR pathway regulates the expression of SOX4 in prostate cancer progression
Schematic model of signaling pathways implicated in tumor cell vascular mimicry (VM)
Diagram is drawn based on published literatures
a ∣ The role of DAP12 and FcRγ in osteoclasts
MicroRNA genes are transcribed from intergenic or intragenic regions of noncoding RNA transcripts mediated by RNA polymerase II, called primary miRNAs (pri-miRNA)
A Microtubules (in blue) are dynamic polymers that form a radial cytoskeleton (left), a bipolar mitotic spindle (center) and the linear axoneme of cilia (right).B Tubulin is a GTPase.
IPA generates networks based on the Ingenuity Knowledge Base that relies on known biological relationships among genes
The recognition of damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS), by Toll-like receptors (TLRs) and other pattern recognition receptors drives the activation of dendritic cells (DCs) and macrophages
(a) Heat-dependent interelukin-6 (IL-6) trans-signalling is initiated by... (b) Febrile temperatures act on lymphocytes and high endothelial cells (...
Schematic model recapitulating the role Shoc2 plays in controlling ERK1/2 activity
UVB activates mTOR pathway through PI3K/Akt signaling, while apigenin inhibits UVB-induced mTOR activation mainly by AMPK, further induces autophagy and suppresses cell proliferation
(a) A broad range of functions can be rapidly d... (b) In T and B cells, Mg2+ is regulating Ca2+ m... (c) Zn2+ is involved in the recruitment of kina...
IGF-1 acts on its receptor to initiate several pathways responsible for protein translation, which in turn aids in cell growth, migration and differentiation
IGF-1 receptor activation mediates cell survival via several pathways, including inhibition of apoptosis via three pathways shown below
Insulin and insulin-like growth factor signalling (IIS) is triggered by binding of the insulin receptor (InsR) or insulin-like growth factor 1 receptor (IGF1R) and activation of an adaptor protein, which can be one of three or four IRS proteins in mammals or the Chico protein in Drosophila fruit flies
The EGFR is a growth factor receptor well known for its capacity to induce mitogenic stimuli
Caveloae could sense and respond to myocardial I/R stress via (1) activating various GPCR-coupled kinases signaling pathway; (2) changing activities of ionic or substrate channels/transporters (“O”); (3) activation and translocation of specific caveolae-associated signaling molecules (“N”) such as eNOS; (4) sensing mechanical stress and plasma membrane repair (“M”)
Major cellular mechanisms controlling contraction in gastrointestinal smooth muscle cells
Potentially drug targetable pathways associated with clear cell RCC include chromatin remodeling and altered tumor metabolism
Loss of fumarate hydratase (FH) is associated with the familial form of type 2 papillary RCC and results in the activation of several pathways
TRAF6 in T lymphocyte activation and differentiation
The SMAD and signal transducer and activator of transcription 3 (STAT3) pathways are the main known regulators of transcription of the gene encoding hepcidin (HAMP) in response to iron-related and inflammatory signals
The epigenetic and transcriptional regulator MeCP2 controls the expression of hundreds of different proteins, including BDNF
Prolonged stress and depression is known to cause atrophy of spine and synapses in brain regions implicated in depression, notably the prefrontal cortex and hippocampus
Intracelluar trafficking pathways are shown for Mycobacterium tuberculosis (Mtb), Chlamydia (Chl), Brucella (Br), and Coxiella burnetii (Cb)
The TNFR1-driven pathway is depicted here, though the regulatory mechanisms shown generally apply to Fas, TRAIL receptor, and TLR-driven necroptosis
Obesity-linked metabolic pathways susceptible to diet induced epigenetic perturbation
Lipotoxicity during NASH activates DR5 proapoptotic signaling cascade activating ROCK1, which promotes release of TRAIL-bearing EV from hepatocytes
pDCs sense DNA viruses, synthetic CpG oligodeoxyribonucleotides (ODN) and endogenous DNA through TLR9
AP-1, activator protein-1; CALM, calmodulin; CBP, cAMP response element-binding protein; CD14, cluster of differentiation; HMGIY, high-mobility group protein; IŒ∫-B, inhibitor of kappaB protein; IFNγ, interferon gamma; IFNGR, interferon-gamma receptor; IŒ∫B-NFŒ∫B, inhibitor of kappaB protein-NFkappaB; IKK, inhibitor-of-kappaB-protein kinase; iNOS, inducible nitric oxide synthase; IRAK, interleukin-1 receptor-associated kinase; IRF1, interferon regulatory factor-1; JAK, janus kinase; LBP, lipopolysaccharide binding protein; LPS, lipopolysaccharide; LY96, lymphocyte antigen 96; MyD88, myeloid differentiation primary response 88; NF-Œ∫B, nuclear factor-kappaB; NO, nitric oxide; p38MAPK, p38 mitogen-activated protein kinase; STAT1, signal transducer and activator of transcription 1; STAT1 dimer, signal transducer and activator of transcription 1 dimer; TAB1, transforming growth factor-beta activated kinase 1; TLR4, toll-like receptor 4; TRAF6, tumor necrosis factor receptor-associated factor 6
LIF/JAK/STAT3 signaling pathway in mouse ESC self-renewal
Canonical Wnt/β-catenin signaling pathway in mouse, rat and human ESC self-renewal
FGF signaling pathway in mouse, rat and human ESC self-renewal
Activin/Nodal signaling pathway in human ESC self-renewal
(A) The principal component analysis (PCA) in which each sphere represents the result from an individual sample (chip) with the plotted location based upon the grouping of each sample relative to the others is shown
a | TNF receptor 1 (TNFR1) signalling is activated by both soluble and transmembrane TNF
The diagrams of the Hippo signaling pathway in (A) Drosophila melanogaster and (B) mammals highlight the core kinase cascade and upstream regulatory signals
mTORC1 consists of mTOR, regulatory associated protein of mTOR (Raptor), Akt/PKB substrate 40 kDa (PRAS40), mammalian lethal with SEC13 protein 8 (mLST8), Tti1/Tel2 complex and DEP domain containing mTOR-interacting protein (Deptor)
mTORC1 signaling promotes the main steps of adipogenesis, including lineage commitment, clonal expansion and terminal differentiation of preadipocytes to mature adipocytes, through S6K, C/EBP-β and -Œ¥, 4E-BP, Lipin1, and PPAR-γ, respectively
ONC201 appears to up-regulate ATF4 translation through a mechanism involving ŒºORFs of the ATF4 gene that partially resembles that used by the classical ISR and UPR
Succinate and Œ±KG accumulation and signaling via GPR91 and GPR99 in response to cell or mitochondrial stress
Pathway analysis based on Ingenuity Pathway Knowledge Base
Molecular pathways of proliferation, survival and senescence
Role of RGS proteins in selected GPCR signaling in bone
Schematic representation of known redox-sensitive signalling pathways which regulate cellular aging and age-related CVDs
Summary of the effects of hypertension, atherosclerosis and PAH on age-related redox-sensitive signalling pathways linked to the different vascular cells comprising the vessel wall (intima: endothelial cells; media: VSMCs; adventitia: fibroblasts/myofibroblasts) as a consequence of Nox-derived ROS
Calpain-1 is rapidly stimulated by the calcium influx generated by NMDA receptor activation, resulting in spectrin and PHLPP1β (SCOP) degradation
Rho Family GTPase signaling pathway alterations in adenoid cystic carcinoma
(a) The isoprenoid biosynthetic pathway with targeted inhibition by statins, nitrogenous bisphosphonates, and novel compounds DGBP and GGOHBP
A schematic model of RIP1-mediated regulation of the PI3K-Akt pathway
APP is synthesized in the ER and gets transported to the Golgi apparatus where it is packaged to vesicles (orange circles) for delivery to the cell surface (Step 1.).
A summary of the intracellular signaling cascades that occur within neurons and glia within the brain
Fatty- acids, glucose and ketone bodies are internalized through surface receptors and can be metabolized into acetyl-CoA through β-oxidation, glycolysis or ketolysis, respectively
An integrated view of therapeutic strategies targeting the transcriptional network and signaling pathways promoting neuronal mitochondrial biogenesis
a | Genome-wide inverted Alu repeats in introns and in 3′ untranslated regions (UTRs) form intramolecular RNA duplexes (Alu dsRNAs), which are edited by adenosine deaminases acting on RNA (ADARs)
Schematic representation of TLR and NLR pathways driving pro-inflammatory state after exposure to extracellular and Intracellular microbial products
(A) Ingenuity Pathway Analysis (IPA) illustrating genes upregulated (red... (B) IPA illustrating genes upregulated (red) and downregulated (green) P...
Schematic of serpinin/pGlu-serpinin formation, its signaling pathway and PN-1-dependent biogenesis of secretory granules in (neuro)endocrine cells
Additional and non-obvious functions of apoptotic cells
A model PAS kinase activation and function in S
The top two networks identified by Ingenuity Pathway Analysis based on qPCR-expression data were merged
Metabolic pathway of P2Y12-receptor inhibitors
On stimulation with taste receptor agonists, the G-protein subunits GŒ±-gustducin and Gβγ dissociate from the G-protein coupled receptor
The complex roles of Wnts in cartilage homeostasis and disease
A. Presynaptic glutamate release and depolarization of the postsynaptic neuron lead to calcium elevation in the postsynaptic cell.
The NO-GAPDH-Siah1 cell death cascade in neurons
GAPDH nitrosylation pathway mediates cocaine effects
Simplified summary of key elements involved in insulin signal transduction that ultimately regulate multiple cellular processes
(A) Proposed pathways in rod-mediated reactivation of end-stage dormant... (B) Txnip as a regulator of glucose metabolism to fatty acids. See text...
H295R WT and ORP2kd cells were cultured into 100 mm dishes treated for 48 h with 0.4 mM Bt2cAMP media collected and the amounts of steroids quantified by ultra performance liquid chromatography tandem mass spectrometry as described in Materials and Methods.
Pathways involved in physiological and in pathological cardiac hypertrophy actuated in calcific aortic valve disease (CAVD)
LGGs arise from mutations in genes whose protein products regulate RAS pathway signaling
Circles represent chance events whereas triangles represent outcomes that lead to recursive, Markov model () – Death, VTE recurrent, VTE no AC, VTE acute
(A) Prior to and during gastrulati... (B) High BMP and WNT signaling alo... (C) The neural border is induced b... (D) Attenuation of BMP and WNT sig...
Many oncogenic mutations drive nutrient transporter gene expression [–]
Disrupted functions in dopamine receptor-, GABA receptor-, and NMDAR-mediated neurotransmission are commonly suggested to contribute to schizophrenia etiologies
The figure shows signaling pathway that may be targeted by diabetic medications on epithelial cells (keratinocytes), vascular endothelial cells, “classically activated” M1-like macrophages, and “alternative activated” M2-like macrophages present in chronic wounds
Schematic depicting the Arg-auxotrophic response
PTH stimulates Rankl and Cox2/PGE2 in osteoblast (OB) lineage cells
G-protein–coupled receptor (GPCR) signaling in platelets
Neuronal electrical activity includes generation and propagation of axonal action potentials through opening of depolarizing Nav and hyperpolarizing Kv
Protein interaction networks incorporating transcriptomic, proteomic and phosphoproteomic data for proteins related to the actin cytoskeleton (A), phospholipid metabolism (B), autophagy (C), glycogen and trehalose metabolism (D) and the cell wall integrity pathway (E)
Core elements of the human EGFR–MAPK pathway
Sfrp2 binds and inhibits Wnt6 signaling through the canonical pathway leading to cell cycle arrest
Model for quantitative regulation by the TCF/β-catenin asymmetry pathway
(a) During corticostriatal pathway activation glutamate is released into... (b) Ascorbic acid release from astrocytes and ascorbic acid uptake is im...
Mechanical force induced AT1R activation and downstream effects
Cyclin–CDK complexes display opposing roles in controlling mitochondrial function
SIRT1 deacetylase is stabilized and activated through multiple mechanisms downstream of BCR-ABL in CML (left) and FLT3-ITD (center) signaling in FLT3-ITD+ AML
Signaling pathways involved in SSc pathogenesis that may also play a role in EndoMT
Schematic representation of involvement of the prohibitin (PHB/PHB1) in granulosa cell (GCs) survival and differentiation functions
Neuroendocrine pathways regulate stress tolerance in C
a | Analogous to the case for β-catenin, p120 catenin isoform 1 is stabilized in response to WNT signalling
Summary of the most important metabolic mechanisms proposed to occur in both cancer and Sertoli cells (SCs)
Diagram summarizing the PI3K/Akt/mTOR axis signaling pathway leading to the nucleation and formation of the phagophore to initiate the autophagy-lysosomal pathway
In rat pancreatic acinar cells CCK-induced PAK2 activation is mediated by activation of CDC42/Rac1, Src and PKC []
Central Metabolism probed by hyperpolarized 13C enriched precursors
Nodes represent molecular entities (proteins, small molecules, mRNAs) and edges represent activating and inhibitory relationships between nodes
The color of the node indicates the node‚Äôs stabilized state: Black node = OFF; White node = ON
Different members of different tick protein families target the same host immune function, or the same protein targets different modules of the host immune response
Trk receptors, such as the NGF receptor TrkA, the gp120 protein, which transduces IL6 signals and GPCRs responsible for detecting inflammatory mediators are capable of signaling via mTORC1 and MAPK pathways in nociceptive DRG and/or TG neurons
Genomic pathway (1): E2 directly activates ERŒ± and ERβ, which bind to the estrogen-response-element (ERE) of gene promoters and induce target gene transcription
The microRNA network that is involved in regulating myogenesis
Heirarchical model of the PCP signaling pathway
Signaling pathways frequently deregulated in MDS
Mechanisms of poor tumor T cell infiltration
Scientific rationales of potential therapeutic combinations with PD pathway blockade
(A) Schematic of androgen synthesis and pre-rec... (B) Differential changes in steroidogenic enzym... (C) Altered expression of genes mediating DHT p...
The effects of alcohol, smoke, obesity, diabetes and hereditary factors on the development and progression of recurrent acute pancreatitis, chronic pancreatitis and pancreatic cancer through increased levels of inflammatory molecules mediated by the PI3K pathway
Decorin induces autophagy in endothelial cells
During the HR process, once resection occurs, homology search and DNA-strand invasion generate D loops, a key intermediate for all subpathways of HR
(A) In the case of a HR defect, such as mutations in BRCA1/2 genes, Polœ... (B) At the same time, PolœÖ is recruited to DNA damage sites by PARP1 wh...
Mechanisms of glucose stimulated insulin secretion (GSIS) and suggested stimulus/secretion coupling factors
An overview of different signaling pathways activated by high glucose ambience, which leads to an altered expression of various ECM glycoproteins, and of genes relevant to EMT and apoptosis processes
Schematics depicting potential mechanism(s) by which high glucose induces ECM glycoprotein synthesis via the activation of small GTPases, Ras or Rho, in diabetic nephropathy
Comparison of the known purinergic signaling pathways of animals to a hypothetical pathway in plants
Processes involved in generation of the T cell-inflamed tumor microenvironment phenotype
Model for how tumor-intrinsic β-catenin signaling mediates exclusion of T cells from the tumor microenvironment
The mTOR pathway is a conserved signaling cascade that results in various fundamental cellular processes, such as autophagy and protein translation
Schematics of the inside-out signaling of integrin activation
(Adapted from Alinari, Quinion, and Blum
Copper is reduced from Cu2+ to Cu+ by a putative cell-surface reductase
Initial contraction and MLC20 phosphorylation induced by LPA involves Gq-dependent PLC-β activation, IP3 generation, Ca2+ release and Ca2+/calmodulin-dependent activation of MLCK
a | Various transcription factors regulate sirtuin expression
Red arrows indicate activating effects whereas blue bars denote inhibiting functions
IPA canonical pathway Cell Cycle: G1/S Checkpoint Regulation with up-regulated genes in the IR-induced common translatome highlighted in pink
The “immune barrier hypothesis” posits that the chronic inflammation associated with CRS is linked to a defective mechanical and innate immune barrier
Currently, two discrete normal colon to colorectal cancer sequences have been identified
Altogether, our findings are summarized in
Cytoskeletal tension is dependent on many factors, including the material properties of the ECM (e.g.
This schematic depicts sex differences in the CRF1 receptor
Top. PPN cells with only P/Q-type calcium channels (20pct) are assumed to be “Wake-on” and modulated by CaMKII (left side, blue channels).
Genes in the MAP kinase signaling pathway (MAPK signaling pathway) identified using the KEGG-based pathway visualization tool
The lifecycle of cardiac Nav1.5 and potential phenotypic modifiers
Schematic graph shows the potential roles of Akt/GSK-3β signaling in DA and NE modulation of synaptic functions in the PFC
Overview of the lysosomal–autophagy pathway
Reactions colored by the shift (absolute value) in flux in a top-producing strain, I3, compared to wild-type in different pathways in central carbon metabolism: (a) the pentose-phosphate pa... (b) glycolysis/gluconeoge... (c) TCA cycle. Sho... (d) are significant reaction flux shifts (p < 0.05) corresponding to various reactions in these pathways in phase I (0–6 hrs) and those for phase II (6–20 hrs) are display...
In the presence of metabolic stress, there is more glucose (Glc) or fatty acids (FAs) being oxidized in the TCA cycle in β-cell mitochondria, which pushes more electron donors (NADH and FADH2) into the electron transport chain (ETC) resulting in more ROS production
Depicted is the initial recognition event in the formation of an immunological synapse between T cells and TAA-expressing target cells, mediated by T cell redirecting BsAb
The gut microbiota is separated from the intestinal epithelium by a thin layer of mucus, secreted by Goblet cells in a microbiota- and NLRP6-dependent manner
Alcohol consumption increases intestinal permeability resulting in increased influx of LPS into the liver
Apoptosis suppresses necroptosis via caspase-8 cleavage and inactivation of RIP1 and RIP3
A. The SHH ligand patched 1 constitutively represses SMO, allowing the sequential phosphorylation of Gli by protein kinase A (PKA), glycogen synthase kinase 3 beta (GSK3B), and casein kinase (CK).
a Radiation induced activation of canonical and non-canonical hedgehog (Hh) signaling pathway
Deletion of ERŒ± in uterine epithelial cells leads to infertility, however, this receptor loss does not prevent estrogen induced epithelial cell proliferation ()
The role of miR-155 on virulent (green) and avirulent (yellow) Mycobacterium species infection in macrophage
Schematic representation of the mammalian target of rapamycin (mTOR) signaling pathway and crosstalk with the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K) pathway
The insulin signaling pathway, which includes AMPK and mTOR, is one pathway that regulates protein synthesis initiation
SOX9 is downstream effector of ERG and AR in TMPRSS2:ERG fusion-positive PCa
(A) Depiction of the pathway in steady state. Receptor tyrosine kinase (... (B) MK-2206 inhibits both AKT and downstream mTORC1 activity. As a conse...
Cell-cycle entry regulated by a network of protein regulators
Upon infection viral ligands (ss/ds RNA/DNA, RNA/DNA hybrids, glycoproteins) are detected by host viral sensors (PRRs, TLRs, ALRs, NLRs) which signal through STING and MAVS to activate IRFs and NFkB, which in turn move in to nucleus, bind to IFN promoter and drive IFN expression
Effect of HDACI on cell survival signaling pathway in hemorrhagic shock
Overview of AR-mediated signalling pathways
Tamoxifen directly inhibits the mitochondrial electron transport chain at complex I
Schematic representation of nodes of therapeutic blockade in the PI3K and other signaling pathways that synergize with BET inhibition
After radiotherapy, there are numerous potential targets within the tumour microenvironment (TME) whose modulation may lead to radiosensitisation
A) Oxygen-dependent regulation of HIF-1α/HIF-2α
A). In T cells, antigen-dependent activation of the T cell Receptor (TCR) signals through the PI3K pathway to stimulate increased translation of HIF-α mRNA.
Schematic representation of the ras signaling pathway
Signal transduction from G-protein-coupled receptors and integrins
The biological function of extracellular HMGB1 is redox dependent
Reciprocal antagonism by TLR4 oncogenic and TGF-β tumor suppressor pathways
Glutathione metabolism pathway in the cytoplasm and in extracelluar space
PcG proteins regulate chromatin structure through post-translational modifications, particularly histone tail methylation
Interaction network of 135 SNO-modified proteins identified in WT and AD mouse brain tissues
PP2A positively and negatively regulates the Wnt signaling pathway
PP2A negatively regulates the mTOR signaling pathway
PP2A positively and negatively regulates the MAPK signaling pathway
(a) Dynamics of CTLA-4 expression and membrane cycling
Summary of mechanisms regulating FGF gradient formation: FGF ligands from the source cell are bound by HSPG side chains to prevent their diffusion farther away from the source tissue
The metabolic map of PI3K-AKT signaling cascade demonstrating potential points regulated by exercise, providing an example of interdependent regulation of signaling cascades by exercise
Regulation of metabolic processes downstream of mTORC2, with major known substrates and metabolic processes highlighted
A model illustrating the different metabolic pathways driving the ccA (orange) and ccB (blue) subtypes
The regulations of mTORC1 and mTORC2, and the major roles of mTORC1 and mTORC2 in mammalian cells
The pathway of miRNA synthesis and its function (top)
Nuclear translocation of GRK5 occurs via stimulation of the Gαq pathway following pathologic stimulus such as transaortic constriction (TAC) or phenylephrine (PE) stimulation
Recognition of ligands by Toll-like receptors (TLRs) leads to signalling via the adaptor MyD88 and subsequent NF-κB activation
In the intrinsic pathway of apoptosis, mitochondrial DNA (mtDNA) is released owing to mitochondrial outer membrane permeabilization mediated by the pro-apoptotic effector proteins BAX (BCL-2-associated X protein) and BAK (BCL-2 antagonist/killer)
Schematic diagram of the major TGF-β signaling pathways in vascular cells
The results suggest that P-gp overexpression not only increases EPI efflux, but also increases Beclin 1 expression and induces autophagy in EPI-R cells
Natural products as TLR agonists and antagonists affecting various stages in the signaling pathway, including downstream molecules MyD88 and IKK
During initial TCR-mediated activation of resting Tregs, signals via the Akt and mTOR pathways can potentially destabilize the Tregs and cause reprogramming into a pro-inflammatory helper-like phenotype (“ex-Tregs”)
a. The roles of EZH2 mediated transcriptional silencing are context specific.
Upon cytokine binding, JAK2 molecules are recruited to cytokine receptors and phosphorylated, with subsequent recruitment and phosphorylation of STAT proteins
(A)During homeostasis most satellite cells are quiescent
Schematic of the pathway of EGF induced anticipatory UPR activation
Genes represented in the 38-gene DTC panel and their biological pathway associations
Schematic of the TGF-β signaling pathway and how a dominant negative TGF-β type II receptor lacks the cytoplasmic domain necessary for TGF-β signaling
Horizontal inhibition refers to targeting of signaling members within different pathways, such as combinations of MEK/AKT, MEK/PI3K, MEK/CDK4, and MEK/Plk1
Actionable drugs in proliferation pathway that have been evaluated in BRAFmut CRC
Trophoblast cells sense infectious pathogen-associated molecular patterns (PAMPs) expressed by bacteria, viruses, fungi and parasites through their expression of Toll-like receptors (TLRs) and Nod-like receptors (NLRs)
Diverse extracellular signaling pathways are regulated by A disintegrin and metalloproteinase (ADAM)-mediated shedding events
mTORC1 is composed of mTOR, regulatory associated protein of mTOR (Raptor), G protein β-subunit-like protein (GβL), proline-rich Akt substrate of 40 kDa (PRAS40), and DEP domain-containing mTOR-interacting protein (Deptor)
Effect of diabetes and KU-596 therapy on the TNF network in dorsal root ganglion
Local innate immune activation or tissue stress can initiate a cytokine milieu capable of stimulating nearby memory T cells in the absence of TCR ligation
To determine which TNF receptor was driving the migratory phenotype, expression of key pathway genes was measured in response to TNFŒ±
The tissue factor (TF) and contact activation pathways lead to a common pathway that generates thrombin
New model for phrenic LTF with multiple molecular pathways
Integration of the genome-wide association studies (GWAS) and RNA-Seq results with known aortic valve stenosis (AS)–related biological processes
Left: CMA participates in the regulation of glycolysis by controlling levels of glycolytic enzymes and enzymes involved in the TCA cycle
mTOR per se is a Ser/Thr protein kinase as noted by the two lobes KD called the KD N-lobe and the KD C-lobe
In this network map, ITGB4 is connected to laminins (LAMA1, LAMB1, LAMC1, LAMA2, etc), genes in the EGFR family (EGFR, ERBB3), genes in the PI3K pathway (PIK3CA, AKT1), other integrins (ITGA6, ITGB1), stem cell markers (CD44, ITGA6) and the tetraspanin CD151
Proposed steps in the PIK (A) and TMC (B) polyketide biosynthetic pathway
ACE-mediated generation of Ang II results in activation of various signaling pathways in cardiomyocytes, cardiac fibroblasts, and endothelial cells, resulting in adverse cardiac remodeling and cardiac dysfunction
Schematic diagram depicting a single pathway from hyperglycemia to TGF-β and multiple pathways from insulin resistance to PIIINP.BMI: Body Mass Index, PIIINP: Procollagen type III N-terminal propeptide, PKC: Protein Kinase C, TGF-β: Transforming growth factor-βSquares indicate fibrosis biomarkers of interest
The proposed schematic of possible mechanisms of metabolic regulation of tumor cells by dysfunctional adipocytes in obesity The major consequence of obesity is adipose tissue inflammation and associated increases in circulating levels of lipolysis-generated lipids and pro-inflammatory cytokines and adipokines
A brief summary of lipid metabolism signaling including fatty acid synthesis and components of the mevalonate pathway thought to be important in the pathogenesis of cancer
Oncogenic survival signaling components in PCNSL
Upon phagocytosis of bacteria, two vesicular pathways are mobilized to greet the bacterium-containing phagosome
(A) A negative feedback loop, in which integrin beta3 expression is indu... (B) In the tumor microenvironment, integrin beta3 signaling is a negativ...
Unique mouse microarray gene IDs involved in Jak/Stat signaling that overlap with human JAK/STAT gene IDs with known interactions with BPA in The Comparative Toxicogenomics Database are shown in red
Unique mouse microarray gene IDs involved in Mapk signaling that overlap with human MAPK gene IDs with known interactions with BPA in The Comparative Toxicogenomics Database are shown in red
The cartoon shows various sources and sinks for Ca2+ in cells
Ingenuity Pathway Analysis™ was used to examine expression of 488 significant genes from neonates with and without histologic chorioamnionitis exposure
Schematic respresentation of the mechanisms of intracellular actions of dynamic tensile strain
(A) M2a polarization. Ligands IL-4 and IL-13 ac... (B) M2b polarization. IL-1R ligands or immune c... (C) M2c polarization. IL-10 and glucocorticoids...
Schematic presentation of mechanisms of actions of CTS
Schematic representation of the mechanisms of intracellular actions of CTS showing CTS suppresses IL-1β induced proinflammatory gene induction by intercepting salient steps in the NF-Œ∫B signaling cascade to inhibit its transcriptional activity by: (i) suppressing IL-1β-induced TAK1 activation and thus phosphorylation and activation of IKK. The suppression of IKK activity results in the inhibition of phosphorylation and proteosomal degradation of IŒ∫BŒ± and IkBβ, thus inhibiti... (ii) During the initial 30 min, CTS up-regulates IŒ∫BŒ± nuclear translocation to prevent NF-Œ∫B binding to the DNA and facilitates export of nuclear NF-Œ∫B, that may enter the nuc... (iii) CTS represses IL-1β-induced IŒ∫BŒ± and IŒ∫Bβ mRNA expression to the control levels and also prevents NF-Œ∫B DNA binding. Collectively, these actions of CTS inhibit proinflammatory gene induction and molecules involved in the regulation of NF-Œ∫B signaling cascade. The red dots indicate steps within the NF-Œ∫B pathway that are inhibited by CTS. The green dots indicate molecular events within the NF-Œ∫B...
Canonical signal transduction cascades in preclinical models of despair and major depressive disorder
A) A pharmacologically addressable response network is shown. By inhibit... B) Regulation of the mTOR pathway by a naphthalimide compound. REDD1 (DD...
Pattern recognition receptors such as TREM-1 and TLR4 can recognize both exogenous (LPS) and endogenous (HMGB-1) signals
T-cell activation is regulated by antigen presentation, as well as stimulatory and inhibitory co-receptors
VEGF-A binding to VEGFR2 activates intrinsic tyrosine kinase activity of the receptors resulting in their transphosphorylation, recruitment of Src and subsequent phosphorylation of VE-cadherin by Src in the junctional complex
mTOR is a serine/threonine kinase that regulates protein synthesis necessary for cell growth, proliferation, metabolism and angiogenesis
A. PC and PE syntheses by the Kennedy pathway.
In the osteocyte, β-catenin is essential for 1)
Overview of the mTOR pathwayAbbreviations: 4E-BP1, 4E-binding protein-1; eIF-4E, eukaryotic initiation factor-4E; EGFR, epidermal growth factor receptor; ER, estrogen receptor; HER2, receptor tyrosine-protein kinase erbB-2; IGF-R1, insulin-like growth factor 1 receptor; IRS, insulin receptor substrate; PRAS40, proline-rich Akt substrate 40 kDa; PTEN, phosphatase and tensin homolog; S6, 40S ribosomal protein; S6K1, S6 kinase 1
RAS-mediated signal transduction pathways and post-translational modification of RAS
Canonical Notch signaling was activated through cleavage by TACE and γ-secretase and release the Notch intracellular fragments (NIC)
Under normal conditions, p120 binds E-cadherin, stabilizes junctions (A), and suppresses inflammatory signaling pathways (B)
Phenotypic pathway of hepatic stellate cells (HSCs).Hepatocyte damage causes an inflammatory reaction which leads to activation of hepatic stellate cells (HSCs)
(Left) Position of individual GBPs or the Gbpchr3−/− deletion encoding 5 clustered family members (GBP1, GBP2, GBP3, GBP5, GBP7) within the canonical NLRP3 and AIM2 inflammasome pathways after type I and II IFN signaling
Mechanism of polyphenols' antioxidant properties
Curcumin and PKC signaling pathway in colon cancer
Proposed signaling pathways and outcomes after stroke and administration of wt tPA or tPA-A.296-299 wt-tPA drives pathway toward the right leading to damage whereas tPA-A296-299 drives pathway towards the left and providing protection
Activated cells take up large amounts of glucose and glutamine and divert them to the pentose-phosphate pathway (PPP) and lipid biosynthesis, respectively
Four representative, simplified signaling pathways are shown
Schematic representation of the PI3K/PDK1/AGC signaling pathway underlying the different mechanism of AKT and other AGC substrates activation by PDK1
Following myectomy injury, Fgf signaling promotes myocyte cell reprogramming and dedifferentiation by activating caspase 3, among others
Accumulation and transcriptional activation of p53 occurs in response to a wide variety of insults such as DNA damage, oxidative stress, excitotoxicity, etc
Major cellular events of GPCR signaling and trafficking
`G protein-dependent' signal control from intracellular membranes
Proposed model for `multi-phase' GPCR signaling organized by the endocytic pathway, using the β2AR as an example
The actions of IL-21 on T cells are context-dependent and shaped by cellular and environmental parameters
Microarray and bioinformatics analysis of tendon fibroblasts treated with PRP or PPP
A) In Xenopus oocytes, testosterone binding to... B) In Sertoli cells, testosterone binds to clas... C) In prostate cancer cells, androgen induces t...
Figure 1a: Cholesky decomposition illustrating the association between Parental Monitoring (PM) and Drug Initiation (DI) in which the sources of covariance between PM and DI are decomposed into shared genetic (a2,1) and environmental (c2,1 & e2,1) effects
AVP stimulation of V1AR on CM leads to enhanced protein synthesis and cellular hypertrophy in phospholipase C (PLC)-protein kinase C (PKC)-dependent increases in calcium and c-fos
In response to DNA double-strand breaks (DSBs) or replication fork collapse (not shown), sensors (light blue) detect the damage, and signalling mediators recruit or activate effectors that repair the damage and activate cell cycle checkpoints
(A) In chordates, echinoderms, platyhelminths,... (B) In nematodes, the anti-apoptotic Bcl-2 prot... (C) In Drosophila, the APAF1 homolog appears to...
When complement encounters a foreign cell, the recognition molecules C1q, mannose-binding lectin (MBL), ficolins, and collectin-11 sense antibody clusters or pathogen-associated molecular patterns (PAMPs) and activate associated serine proteases (C1r, C1s or MBL-associated serine proteases (MASPs)) that cleave C4 and C2 to form the C3 convertase (C4b2b) of the classical pathway (CP) and lectin pathway (LP) on the triggering cell
IPA software uses pathway information to identify potential upstream regulators that could explain the observed pattern of gene expression
Activation of “RNA-sensing” TLRs on neurons and microglia triggers distinct effects
Roles of the PtdIns(3,4,5)P3/Akt pathway on insulin signaling in liver fat and muscle tissue with representative substrates indicated
Figure describes the various roles of IL-15 in CD immunopathogenesis
CAR targeted miRNA and mRNA in liver cancer
Direct Activation – CAR is sequestered in a cytoplasmic complex containing HSP90 and CCRP
In Tconv, NFAT and RAR cooperate to upregulate CCR9 and α4β7 independently of mTOR activity
A model deciphering the signalling pathway hijacked by EspT leading to induction of inflammatory responses in macrophages
Activation of PAR1 by α-thrombin (α-Th) promotes rapid coupling to heterotrimeric Gαq and Gα12/13 proteins comprised of α and βγ subunits
Diagram of the role of GSK3β in skin tumorigenesis
Schematic presentation of the molecular and blood pressure responses elicited by peripheral NMDAR activation
In left panel, the hexosamine pathway controls O-GlcNAcylation of nuclear and cytoplasmic proteins
Schematic illustration of intracellular and intercellular signaling and cellular dynamics in bone healing and bone remodeling
A. CyaA binds to the bent form of the CR3 receptor.
(a) Multiple insect viruses encode... (b) Apoptosis triggered in infecte... (c) In insects, translation is inh... (d) Regulation of the insect IMD/N...
The RIG-I-like receptors RIG-I and MDA5 are activated by viral dsRNA in the cell cytoplasm
Intracellular signaling pathways of EET’s
Enriched cancer hallmarks generated by dataset integration using TieDIE after inclusion of the phosphoproteomic and gene expression data relative to gene expression data alone (A)
(A) Phosphorylation-based cancer hallmarks using integrated personalized signatures (pCHIPS) analysis for patient RA40 revealed strong enrichment of cell cycle and PI3K-AKT-mTOR pathway networks
Patient-specific networks were developed from the stemness pathway hallmarks and revealed distinct regions of the network were differentially activated across the CRPC patient samples
Polyphenols modulate processes leading to synapse growth and increased receptor density
Activation of diverse pro-survival pathways such as MAPK, PIK3CA-m-TOR and TGF-β in setting of mutant p53 and p16.EMT: Epithelialmesenchymal transition; ERK: Extracellular signal regulated kinase pathway; JNK: Jun N-terminal kinase; PTEN: Phosphotase tensin homolog; PKA: Protein kinase A.
Mechanisms of resistance to RAF inhibitors
(A) Intercellular homeostatic signaling demonstrating; differentiation of CD4 T-cells in a context dependent manner; Regulation of mast cell activation by direct interaction e.g.
Likely pathogenic mutations present in ER-positive/HER2-negative male breast cancers but not targeted by likely pathogenic mutations in ER-positive/HER2-negative female breast cancers from The Cancer Genome Atlas (TCGA) study were annotated using Ingenuity Pathway Analysis (IPA)
Axotomy activates the Wallerian degeneration pathway for the selective elimination and degeneration of severed axons
Resistin binds to TLR4 activating the PI3K pathway
This schematic demonstrates some of the major steps associated with the canonical NF-Œ∫B signaling pathway under both unstimulated and stimulated conditions
NF-Œ∫B inducing kinase (NIK) is constantly being translated
Much of the regulation of the non-canonical NF-Œ∫B pathway revolves around stabilization or degradation of NIK
Pathways involved in physiological and in the pathological cardiac hypertrophy of calcific aortic valve disease (CAVD)
Several independent yet critical neuroadaptations (e.g., decreased DRD2 in DLS, increased NR2C in NAcore, 14-3-3ζ, and neuropeptides in CeA) likely all sustain activity in what could be called the “compulsive network”.
Iron stimulates hepcidin (HAMP) transcription through holo-transferrin (Fe-TF) and BMP6
Agents targeting the BMP/SMAD pathway include: LDN-193189 inhibiting BMP type I receptor activity; soluble hemojuvelin fusion protein (sHJV), heparin, and BMP6 antibody (Ab) sequestering BMP ligands; hemojuvelin (HJV) Ab neutralizing HJV function; and follistatin-315 sequestering Activin B
A) Localization of core components in Drosophila epithelia. Under condit... B) Localization of core components in 32 cell mouse blastocysts. In oute...
Hippo signaling is regulated by levels of F-actin, tension within the actin cytoskeleton, and cell attachments
Effects of immune cell-derived complement on T cell immune responses
A: TGFβ and BMP signalling pathways. To activate signalling, a TGFβ or a... B: Notch signalling pathway. Notch signalling is activated when a signal...
Red represents Notch pathway induced interactions
The studies are for the endogenous production of H2O2
Signaling network that regulates ISC activity in response to injury
Left panel: Palmitoyl-LIMK1 on the dendritic spine membrane is phosphorylated and activated via a pathway that involves membrane-bound upstream activators such as Rac, Cdc42 (which is also palmitoylated) and PAK
TGFβ receptor signaling is initiated by the binding of TGFβ ligands to the TGFβ type II receptor (TGFbRII) to recruit and catalyze phosphorylation of the TGFβ type I receptor (TGFbRI), which subsequently phosphorylates the transcription factors SMAD2 and/or SMAD3
Metabolic pathways and genes involved in the utilization of nonfermentable carbons
Oridonin regulates multi-signaling pathways to display corresponding multifunctional effects
Murine studies have revealed that TCR and IL-2 lead to NFAT and STAT5b binding to the CNS2 locus, stabilizing Foxp3 expression
a | Stimulator of interferon genes (STING)-driven inflammation-associated cancer
Interaction between the canonical WNT signaling pathway and other signaling pathways implicated in MPNST tumorigenesis
Schematic of the Akt/mTORC1 signaling pathway leading to accelerated translation and increased protein synthesis
A model illustrating the involvement of CBP/p300 function as a cointegrator of different signaling
PD and PK pathways of HMGCo A reductase inhibitors (Statins)
Schematic representing intrinsic and extrinsic apoptosis initiation
Mechanisms of CHOP-induced apoptosis under prolonged ER stress
Schematic signal transduction network representing the effect of chronic alcohol on protein balance in eWAT
In the presence of amino acids, growth factors and energy, the mTOR complex represses autophagy by inhibiting the kinase activity of ULK1
A simplified representation of the type I IFN signal transduction pathway
ABT-199 treatment releases Bim from Bcl-2
Schematic representation of the (A) Wnt/β-catenin, (B) AKT/mTOR, (C) ERK/MAPK signaling networks that are important for oligodendrocyte development and myelination
Schematic diagram of the Hedgehog signaling pathway
Schematic representation of the proposed crosstalk between PC1 and calcineurin/NFAT signalling in hPDL cells under mechanical stimulation
The hypoxia-inducible transcription factor (HIF) pathway in clear cell renal cancer
The molecular pathways underlying the development of the male external genitalia
The ligands for MRGPRX2 activate pertussis toxin-dependent GŒ±i and pertussis toxin-independent GŒ±q pathways for MC responses
Factors involved in the ontogeny of fetal Leydig cells
De novo sphingolipid metabolism occurs at the endoplasmic reticulum (ER) and starts with the condensation of palmitoyl coenzyme A (CoA) and serine by serine palmitoyltransferase (SPT), which can be negatively regulated by ORM1-like protein 3 (ORMDL3), followed by series of enzyme catalyzed reactions finally forming ceramide
S1P can combine with five S1P receptors which is S1P1–5
A simplistic view of Hh signal transduction is portrayed in the upper panels
A. Liver-derived, systemically circulating complement can be activated through the classical, lectin or alternative pathway.
Upon cytokine binding, JAK2 molecules are recruited and activated by cytokine receptors, which results in phosphorylation of downstream signaling pathways such as PI3K, RAS, and STAT3/5
Various cellular pathways known to be affected by low dose CO are depicted
A) Gene expression signature is pl... B) Frequency of somatic mutations... C) Impact of DPYD mutations on enz... D) Pathway map shows separation an...
Complement activation is initiated by three pathways (green), converging toward activation of C3, which is further amplified in a positive feed-back loop (blue)
In RTK-driven tumors, essential signals are transduced from the receptor to various kinases
Once L. monocytogenes accesses the cytosol it is rarely exposed to extracellular host defenses, as such, detection by cytosolic innate immune sensors is likely critical for combating infection.
Mutations affecting the upstream oncogenes KIT and PDGFRA were only found in the genital melanoma cases and were not found in any of the genital nevi
Schematic diagram of HGF signaling pathways; A) Representative structures, cMET binding affinit... B) HGF signaling pathways known to be involved in...
(A) Flow chart showing the insulin... (B) Scatter plot showing the disti... (C) Selected examples of dynamical... (D) Protein complex view of the in...
RASSF1A has a complex role in regulating Ras signaling through Raf-1 and AKT, primarily through its interactions with the MST2 and Src kinases and the PP1A phosphatase
Proposed mechanisms by which the interaction of dietary long-chain n-3 polyunsaturated fatty acids from fish oil and butyrate from bacterial fermentation of dietary fiber may reduce colon tumorigenesis
Activators of PLCγ known to activate the UPR are in bold
After acute consumption, fructose is efficiently metabolized by ketohexokinase (KHK) into fructose 1-phosphatase
Key mechanisms of mitochondrial regulation by c-MYC, K-RAS, PI3K and p53 signaling pathways
The proposed mechanism of the priming phase of complement-induced liver regeneration
Four pathways for double-stranded break (DSB) repair.Nascent DSBs are first recognized by ATM and the MRN complex that initiate a series of DNA damage response events that aim at arresting cell cycle and recruiting DSB repair proteins
The DMP1 gene is unique in that it produces both oncogenic (DMP1β) and tumor-suppressive proteins from the single genomic locus
As shown in “A” (left side), inflammatory stimuli, such as carrageenan, IL-6 or TNFα, applied at the terminal of the IB4-positive nociceptor, triggers the events that will lead to the development of Type I hyperalgesic priming
Several candidate susceptibility genes converge on NMDAR complexes either in ligand mediated mechanisms (pre-receptor) or in post-receptor protein interactions
A) Bone-Kidney Endocrine Axis. FGF-23 produced... B) FGF-23 and α-Klotho are also expressed in ac... C) A model of FGF-23 cardiotoxicity derived fro...
Possible orientation of nuclear β-AR signaling complexes
Transport proteins in Alzheimer’s disease
PPAR signaling pathway upregulated in LCMUFA group compared to control (FDR < 0.01) and olive oil group (FDR < 0.01)
Endocrine related Hippo Signaling Pathway
Possible mechanisms underlying AMPKŒ±1 activation via cAMP-ERK1/2-LKB1 signaling pathway in EE-induc ed cholestasis
Biochemical/molecular pathway by which maternal hyperglycemia may cause birth defects
Antigen-BCR binding triggers a signaling pathway in which BTK is recruited to the cell membrane from the cytosol, docks with the linker protein BLNK and phosphorylates PLCγ2, with downstream calcium flux and cellular activation via nuclear translocation of transcription factors NFŒ∫B and NFAT
Pol Œ∫ has three mechanisms: primer synthesis, 9-1-1 recruitment, and Rad17 stabilization
Upon binding of Wnt ligands to receptors such as Frizzled (Fzd) and Ror2, multiple downstream signaling cascades are activated
Scheme of the glycogen synthase kinase-3 (GSK3) signaling pathway modulated by ketamine
After entering the cell, glucose is phosphorylated by HK1 and then most of it is degraded via glycolysis (A) to pyruv... (B) to produ... (C) serves a...
Regulatory pathways of LAB- or lactic acid-induced opaque cell filamentation
This novel signaling pathway is indicated by the solid pink arrow
Rapid-acting antidepressants, including ketamine, LY341495, and GLYX-13 increase phospho-ERK and BDNF release via an activity dependent mechanism
Most cells are protected from TNF-mediated cell death due to the presence two sequential cell death checkpoints that are turned on upon initiation of signaling from TNFR1
Metformin can alter the microbiota in the intestine, resulting a reduction in LPS production and translocation across the intestinal barrier
Interleukin-15 (IL-15), produced by cells of haematopoietic or non-haematopoietic origin, can act on dendritic cells (DCs) — possibly in an autocrine manner if the source of IL-15 is a DC — and endow them with the ability to secrete IL-12 and IL-23 and to promote the differentiation of T helper 1 (TH1) and TH17 cells
Interleukin-15 (IL-15) and non-classical MHC class I molecules are induced on tissue cells by cellular stress
GRK isoforms regulating the signaling of the dopamine receptors in the striatum
Integration of a the polycystin–1 (PC1; Pkd1) and polycystin–2 (PC2; Pkd2) flow sensing complex, and b the TAZ, extracellular matrix, and cytoskeletal dynamics mechanosensing pathway in the regulation of osteoblastogenesis and adipogenesis in response to mechanical cues in the bone microenvironment
Ingenuity pathway analysis of endocrine networks depicted in  through
Oxidative stress intracellular signaling pathways in lung cancer
SNP rs3184504 on human chromosome 12 is associated with autoimmune diseases
Illustration showing how the CaMKII–MK2 pathway may exacerbate hyperglycaemia and hyperinsulinaemia in obesity
In the osteoblastic niche near the bone surface several stromal cells as well as HSC-derived cells regulate HSC function
TLR3 recognizes dsRNA [and analogs, such as poly(I:C)] derived from viruses or virus-infected cells and induces the antiviral immune response by promoting the production of type I IFNs and inflammatory cytokines (for example, IL-6 and IL-12p40) through the TRIF-dependent pathway
In this model, MALT1 protease activity, induced by the thrombin receptor and possibly other related GPCRs including those for histamine and LPA, cleaves microtubule-associated CYLD leading to microtubule instability
As shown below, insulin signaling is a central node that regulates an abundance of metabolic proteins found to be altered in the hippocampus of offspring exposed throughout development to cigarette smoke
(1) Nicotine binds to the nicotinic acetylcholine receptor, causing a conformational change that opens the receptor's ion channel and allowing entry of Ca2+ and Na+
Binding of the ligand to insulin receptor or IGF1 receptor activates the insulin receptor substrate (IRS)
Models for organization of CO2signaling pathways
As shown below, insulin signaling is a central node that regulates an abundance of metabolic proteins found to be altered in the liver of offspring developmentally exposed to cigarette smoke
A simplified diagram of mTORC1 and ERK1/2 signaling following muscle contraction
Schematic representation of the Activin/TGF-β mediated Smad2/3 signaling pathway
CSCs can be separated from differentiated cancer cells and typically express CD47 at a 2‚Äì4-fold higher level
Following stroke or cerebral ischemia-reperfusion injury, complement can be activated by the direct binding of C1q and MBL to stressed cells, or via natural antibodies that recognize danger-associated molecular patterns (DAMPs)
IL-10 promotes a STAT3-mediated anti-inflammatory response characterized by reduced expression of pro-inflammatory cytokines and increased expression of anti-inflammatory targets
A. MCPyV oncoproteins drive cellular transformation through interaction with host proteins.
Osmotic stress and ABA sensing and signaling
Resting immune cells, such as monocytes or T cells primarily produce energy (ATP) from breaking down glucose into pyruvate, and through mitochondrial oxidative phosphorylation
(a) Bacterial toxins, such as TcdB, C3, VopS and IbpA or intracellular cAMP cause inactivation of RhoA and consequently disrupt PKN-mediated phosphorylation of Pyrin, which releases the 14-3-3 protein guards from Pyrin to promote assembly of the Pyrin inflammasome and release IL-1β and IL-18 to support host defense against these bacterial pathogens
Diagram of activation of the RAS proteins (HRAS, KRAS, NRAS), the MEK-ERK signaling cascade, and the PI3K-AKT signaling pathways with annotation of the signaling proteins affected by mutations in histiocytic neoplasms is shown
A double-strand break can be repaired by cNHEJ with minimal end processing
Bold red arrows depict common oncogenic pathways in brain tumors such as the PI3K-AKT pathway, mTOR and MYC activation, and alterations in p53, which impact various aspects of glycolysis
Common oncogenic proteins in brain tumors like the PI3K-AKT pathway, MYC activation, alterations in p53 and mutations in isocitrate dehydrogenase 1 (IDH1) directly or indirectly influence TCA cycle-related, fatty acid or amino acid metabolism (depicted by bold red arrows)
LPS stimulates insulin and leptin secretion in peripheral tissues as well as secretion of other pro-inflammatory cytokines in microglial cells and periphery
A) Apoptotic stimulus activates basolateral actomyosin contraction to sq... B) During normal epithelial turnover, mechanical crowding from cell prol...
Following conversion to arachidonic acid by phospholipase A2, further processing occurs via either the prostaglandin pathway mediated by COX-1/COX-2 or the leukotriene pathway mediated by 5-lipoxygenase
Environmental enrichment regulation of specific Canonical Pathways at the mRNA level (left) and protein level (right)
Cocaine regulation of specific Canonical Pathways at the mRNA level (left) and protein level (right)
Hypoxia enhances the immune response, and is an inflammatory stimulus by itself
Schematic of the PI3K/mTOR signaling pathway
(Pro)renin (PRR) Induces Renal Damage Via cyclooxygenase-2 (COX-2) signaling
NF1 is a novel Gβγ effector downstream from MORs activation and is essential for MORs-induced Ras pathway activation in MSNs
Upper parts of the schematic shows multiple classes of receptors, some that sense a variety of chemical stimuli and others that sense mechanical signals, all of which utilize GIV-GEF to transactivate G proteins
Representative image of wild-type and Tlr8−/− mice cells that are infected with WNV and the proposed mechanism of signaling
Cardiac fibroblasts are not unidimensional matrix-secreting cells, but exhibit remarkable functional pluralism
A two-signal model for NLRP3 inflammasome activation
Mechanisms of activation for non-canonical and alternative NLRP3 inflammasomes
Pro-inflammatory pathway of IL-18 in the maturation and activation of T cell subsets are demonstrated by red arrows and anti-inflammatory pathway by green arrows, and blue arrows indicates that IL-18 has a role in a number of inflammatory cells activation to promote autoimmune and allergic diseases
(A) Redox control of gene expression as explained in the text
Model of the involvement of HSPs and class Ib molecules in immune surveillance and anti-tumor responses
HDAC1 and HDAC2 reportedly activate p53 by deacetylating its K381 and K382 residues, where it leads to an increase in the expression of genes involved in apoptosis, including, Bbc3 (PUMA), and Bim [–]
The different pathway colors are arbitrarily assigned to facilitate visualization
The receptor-mediated (extrinsic) pathway of apoptosis is initiated when ligands of TNF-α family such as FAS and TNF-α bind their plasma membrane-bound death receptors, this binding leads to activation of caspase-8 via TNFR-associated death domain (TRADD) and FAS-associated death domain (FADD) proteins
Schematic of immune signaling cascades triggered by Cryptococcus neoformans recognition
Endocytic mechanisms, namely macropinocytosis, phagocytosis and clathrin-mediated endocytosis, are depicted on the PM
(A) TFEB and MITF localization is dependent on their phosphorylation sites and states
Disorders of the mTORC1 signaling pathway
Moderate, but not excessive, alcohol consumption causes activation of intracellular signalling cascades that lead to the expression of genes encoding growth factors or neuropeptides
Upon TCR stimulation, TCR interacts with peptide-MHC complex presented on antigen presenting cells, leading to the activation of LCK and PI3K
Ingenuity Pathway Analysis of the top overlapping networks in chronic beryllium disease and sarcoidosis
In macrophages, interferon (IFN)-β induces several gene products (miR-342-5p, cholesterol-25-hydroxylase [Ch25h], viperin, interferon-induced transmembrane protein 3 [Ifitm3]) that inhibit virus by depleting cholesterol [CHOL] and isoprenoids required for viral gene expression in the replication organelle, and/or by reprogramming intracellular cholesterol trafficking
Mechanisms of PPAR-Œ¥ mediated gene regulation
Alterations in DLPFC layer 3 pyramidal cells in schizophrenia
After insulin binds to its receptor IR, the receptor phosphorylates and activates IRS-1
Following TNF stimulation, TNFR1 sequentially recruits TNFR-associated death domain (TRADD), FAS-associated death domain (FADD) and caspase-8 leading to Caspase-3 activation and apoptosis
(A) PHD3/EglN3 -mediated prolyl hydroxylation o... (B) MAPK6 (Mitogen-activated protein kinase (C) RIPK4 hydroxylation by FIH affects RIPK4 ac...
Akt is one of the main effector molecules downstream of PI3K and regulates various metabolic processes by phosphorylating enzymes such as ACLY, which is needed for lipid synthesis, or HK2 and PFK2, which are involved in glycolysis
Glucose is metabolized to pyruvate through glycolysis and can be further converted to lactate, which is then secreted
ROS can be produced in B cells as a byproduct of mitochondrial function and by NADPH oxidases
MAPK signaling and interactions among other hormonal signaling networks shape the amplitude of the jasmonate bursts and downstream signaling
Cancer cells up-regulate both catabolic and anabolic pathways to optimize energy and macromolecule production
Insulin receptor (IR) and IGF-1 receptor (IGF-1R) can either homo- or heterodimerize to activate their TK domains; this stimulates downstream RAS/RAF/MEK/ERK and RAS/PI3K/AKT/mTOR signal transduction pathways, which induce survival, proliferation, angiogenesis and ribosomal synthesis of several proteins, including hypoxia-induced factor 1α (HIF-1α)
In obesity, enlarged adipocytes secrete pro-inflammatory adipokines such as leptin, TNF-Œ±, CCl-2 and IL-6 and localy induce an M1 macrophage phenotype
Alcohol consumption increases gut permeability and facilitates translocation of bacteria-derived LPS from the gut to the liver
Canonical Notch signaling and Notch conservation between human and Monosiga brevicollis
Interleukin-10 (IL-10) gene transcription regulation
NLRP3, NLRC5, NLRP7, AIM2 and other inflammasome-like signaling is activated in response to S
Displays canonical IL-1 signaling pathway identified through Ingenuity Pathway Analysis (IPA)
Displays canonical P2Y Purinergic Receptor Signaling pathway identified through Ingenuity Pathway Analysis (IPA)
Displays canonical BMP pathway identified through Ingenuity Pathway Analysis (IPA)
Implications of cell biological processes on innate immune signaling
The biosynthetic pathway: nucleic acid detection from within the cytosol
Portion of the miRNA-augmented Regulation of lipolysis in adipocytes pathway
Wild-type p53 generally functions to induce circulating glucose level by (A) suppressing glucose uptake; (B) inhibiting aerobic glycolysis; and (C) promoting gluconeogenesis
TGFβ is first captured by TGFβ receptor II (in brown) and TGFβ receptor I or Alk5 (in green) then to form a complex that may activate Smad proteins (left branch) or the Smad independent pathway (right branch)
NO regulates VfHaHK and SiliHaHK autophosphorylation activity and may ultimately influence their symbiotic relationships with their respective eukaryotic hosts
FRC development is incompletely defined, but a series of crucial checkpoints have been identified.a | Lymph node anlagen specification.
The mTOR kinase is a component of two distinct multiprotein complexes called mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2)
Pathways activated following binding of the TSLP cytokine to its receptor complex
Naïve T cells are predominantly oxidative and constantly monitor their environment for immune insult
It is accepted that the major cause of chronic inflammation in the normal, acid-secreting stomach is H. pylori colonization.
AC activation: Extracellular cAMP stimulation of the CAR1/G protein complex mediates Ras activation, which leads to activation of PI3K and accumulation of PIP3
PI3K/PLC-signaling: Upon cAMP stimulation, both PI3K and PLC are activated and both target PIP2
Prohibitin bindings and up/down stream regulations are shown
VSX2WT acts in multiple ways to maintain NR identity
Upon ligand binding the phosphorylation of ITAM (immunoreceptor tyrosine-based activation motif) associated with the adaptor protein DAP12 (DNAX activation protein of 12 kDa) occurs resulting in the recruitment and activation of Syk (spleen tyrosine kinase)
TREM-2 ligand binding activates DAP12 and downstream Syk and ZAP-70 (Zeta-chain-associated protein kinase 70) which in turn activate PI3K (phosphatidylinositol-4,5-bisphosphate 3-kinase) pathway resulting in Ca2+ influx
The genomic locus for HER2 is amplified in ~20 pct of human BCs, and is associated with aggressive disease with shorter overall and disease-free survival []
(A) GIPR is recycled constitutively by the fast TR recycling pathway (black arrows)
a | Apoptosis can be initiated through intrinsic or extrinsic pathways
Model of signaling events leading to MYC and YAP upregulation
IKKε promotes glycolytic-metabolism and pancreatic tumor growth through its regulation of Akt/GSK3β/c-MYC axis
Resveratrol has been demonstrated to be an allosteric activator of SIRT1
A) During EndMT, ECs up-regulate bFGF in response to TGFβ stimulation. b... B) TGFβ signals through a TGFβR1 and TGFβR2 receptor complex, which acti...
Treatment with BEZ235 upregulates MYC via a FOXO/MAPK-dependent pathway (black blunt line, upper left part)
Like all MAPK family members, the SAPKs, JNKs and p38s, are activated by a phosphorylation cascade
Proposed model for the mechanism of SNRK regulation of ROCK activity
CKD-induced TNF-Œ± stimulates myostatin production via NF-Œ∫B
The TLR signaling pathway and ENU-induced mutations that impair TLR-dependent TNF or type I IFN secretion
(a) Condition-specific dependency network (CDN)... (b) CDN for TG-101348-insensitive cell lines. (c) Evidence network for the TG-101348 – DAPK3...
(a) Condition-specific dependency network (CDN)... (b) CDN for indisulam for drug-insensitive cell... (c) Evidence network for the indisulam – HIF1A...
Insulin Receptor Signaling Pathway Targeted by Surgery-Responsive microRNAs
Gene co-expression change of small cell lung cancer pathway under oil+9527 treatmentNote:DAVID () annotation for the high weight genes resulted in the top annotation cluster (with an enrichment score of 7.27) that contains 8 KEGG cancer pathways, e.g., hsa05215:Prostate cancer (p = 5.60E-14), hsa05220:Chronic myeloid leukemia (p = 7.65E-12), hsa05212:Pancreatic cancer (p = 1.61E-10), hsa05223:Non-small cell lung cancer (p = 2.85E-07), etc
Cancer cells are characterized by the “Warburg effect” wherein the cells use greatly increased levels of glucose (indicated by the black arrows throughout the diagram)
Upon binding to their respective receptors, external stimuli result in a signaling cascade that either directly, or indirectly via upregulation of another protein (Y), result in changes in the GR signalling pathway
Pulsatile release of GH may activate Stat5 to induce male-specific Cyp7b1 expression and the alternative bile acid synthesis pathway
Depiction of dysregulated oncogenic receptor tyrosine kinases (RTKs) and intracellular downstream mediators (green boxes)
Rationale for combination therapy in lymphoma
A possible model for the interaction between A
Schematic demonstrating the signaling networks and their cross talks involved in differentiating the mesenchymal stem cells (MSCs) into osteoblasts
Activation of TLR leads to signaling via two principal pathways: MyD88-dependent pathway and TRIF-dependent pathway
Biosynthesis of the lipid-linked oligosaccharide precursor for N-linked glycosylation and known defects in this pathway
TGFβs binds to a common TGFβ receptor complex, and signals through phosphorylation of the canonical TGFβ-specific SMADs (i.e., pSMAD2/3).
Posttranscriptional mechanisms of regulation of the miRNA biogenesis pathway
(A) TGFβ pathway. (B) Mdm2-p53 pathway. (C) NF-Œ∫B pathway. (D) Wnt pathway.
Defective Treg cell suppressive mechanisms in IPEX and IPEX-like disorders
Intrinsic and extrinsic factors used during vertebrate lens development
GAS6 promotes PCa survival by G1 cell cycle arrest/ S phase delay and inhibition of apoptotic signaling pathways during chemotherapy in bone marrow, which may have important implications for targeting metastatic disease
B. abortus PAMPs trigger MAPK and NF-Œ∫B signaling pathways in a MyD88 and IRAK-4-dependent manner which is important in the induction of the first signal and generate inactive form of pro-IL-1β.
Schematized general estrogen signaling pathway
Basic overview of metabolic dysregulation pathways
Double arrow denotes AT1/Nox4 physical association
Multifunctionality of Man-HA-MnO2 NPsaaMnO2 particles (~15 nm) are entrapped in hyaluronic acid (HA) with mannan molecules attached
The EML4-ALK fusion is formed via an abnormal rearrangement on chromosome 2 which juxtaposes part of the N-terminus of EML4 to a portion of the C-terminus of ALK
Schematic summary of metabolic pathways disturbance caused by suppression of pyruvate carboxylase in MDA-MB-231-derived cell lines
Differential gene expression in PPAR signaling pathway
Application of metabolomics methods to the pancreatic islet has resulted in identification of mechanisms that may complement the classical KATP-channel-dependent pathway for GSIS
SRM-based quantification of a protein network in three prostate cancer cell lines, DU145, LNCaP and PC-3, at four time points post-treatment with docetaxel and in untreated controls in comparison to mRNA abundance changes
The canonical Wnt/b-catenin signaling pathway
TGF-b/BMP signaling pathway in osteoblast differentiation
Impact of ELS on the normal development of tissues and organs
a. Primary cilia on progenitor cells the mouse neuroepithelium at embryonic day 10.5 (E10.5) visualized by scanning electron microscopy.b.
The genomic locus for HER2 is amplified in ~20 pct and the protein is overexpressed in ~30 pct of human BCs, and is associated with aggressive disease with shorter overall and disease-free survival []
The de novo purine biosynthetic pathway in humans consists of 10 highly conserved steps (green) that transforms phosphoribosylpyrophosphate (PRPP), generated through the pentose phosphate pathway (blue), into inosine 5‚Ä≤-monophosphate (IMP)
While the exact triggers for purinosome formation are not known, diffusion and protein-protein interaction studies have provided insight into how purinosomes may assemble in cells under purine-depleted growth conditions
Selected agents used for signaling pathway inhibition or for targeting mesenchymalized carcinoma cells via direct or immune-mediated killing
Top: The BH3-only Bcl-2 proteins Bim and Bmf mediate anoikis by activating the intrinsic mitochondrial apoptosis pathway
A) Acute Kidney Injury: MSC EV pro... B) Myocardial Infarction: MSC EV c... C) Liver Injury: MSC EV inhibited... D) Brain Injury: MSCs transferred...
The models show the molecular mechanisms responsible for relocalizing DSBs to sub-nuclear domains to continue repair, including the current understanding of the final destination of these movements, regulatory components of the SUMOylation pathway involved (black, bold), and repair outcomes (blue, italics)
Viruses exploit host proteasome pathway for immune evasion
Viral regulation of host proteins via post translational modifications
A. The Hippo pathway (mammalian) consists of the core components STK3 and STK4, SAV, LATS1 and 2, MOB1A and B, YAP, TAZ, and TEAD.
(A) Cytokines can be made up of multiple subunits. Some subunits are spe... (B) IL23 signaling is mediated by the engagement of the heterodimeric IL...
(A) Mice were randomly divided to control (B) When probed with fracture and control mouse... (C) Proteins that were shown (by LC-MS) to be i...
Model for MYC-mediated mRNA cap methylation of Wnt/β-catenin signaling pathway transcripts
Breast cancer microenvironment is composed of diverse cell types including notably adipocytes, fibroblasts or immune cells, secreting numerous chemoattractant factors such as growth factors, chemokines or cytokines, including IL-6, that sustain cell migration or invasion
Network of the genes related with post-translational modification, cancer, and tumor morphology
Network of the genes related with cancer and DNA replication, recombination, and repair
Fibrous dysplasia (FD) results from post-zygotic, activating mutations in the gene GNAS, which encodes for the GsŒ± subunit of the G protein complex
The functions of natural IgM in homeostasis maintenance and autoimmune diseases prevention; (A) sIgM enhances apoptoti... (B) sIgM prevents the esca...
Membrane-associated APP is processed through non-amyloidogenic or amyloidogenic pathway, resulting in the production of sAPPŒ± (green) and Aβ (red), respectively
a | An example of the extrinsic pathway is depicted, wherein binding of FasL to its cognate death receptor Fas facilitates the recruitment of FADD
Latency reversing agents (LRAs) that induce HIV expression in latently infected cells include histone deacetylase inhibitors (HDACi), bromodomain and extra-terminal (BET) inhibitors, methylation inhibitors and protein kinase C (PKC) agonists
Signaling pathway stimulated by cotinine.Stimulation of Œ±7 nicotinic receptors activates PI3K leading to the activating phosphorylations on Akt, which phosphorylates the inhibitory Ser-9 of GSK3β, leading to pro-cognitive effects
(A) Overlay of our experimental results with ph... (B) String database integration. A protein asso... (C) High-level summary of network organization....
A schematic diagram illustrating the possible interplay between the EGFR and CK2 signaling pathways that regulate GBM cell proliferation
a | Intestinal epithelial cells, particularly Paneth cells, have a well-developed endoplasmic reticulum (ER) to manage their high secretory demands, including the production of antimicrobial proteins such as lysozyme and defensins
a | Inositol-requiring enzyme 1α (IRE1α) activation and subsequent splicing of X-box binding protein 1 (Xbp1) produces the transcription factor XBP1s that directly binds the promoters of tumour necrosis factor (Tnf) and interleukin-6 (Il6)
Schematic of the genes involved in PCP signaling
CD40-CD40L interaction recruits TRAFs (TRAF2, 3, 5 and 6) which bind to the CD40 cytoplasmic domain and mediates the activation of multiple signaling pathways including canonical and non-canonical NFŒ∫B pathways, PI3K pathway, as well as phosphorylation of MAP kinases including P38, ERK and JNK
A. The opening of paracellular pathways: cytoskeletal rearrangements and related signaling in endothelial cells.
LPA-LPA1signaling contributes to the development of renal fibrosis through interactions between tubular epithelial cells and fibroblasts, in which LPA-LPA1signaling stimulates tubular epithelial cells to produce CTGF through a GŒ±12/13-Rho-ROCK-MRTF-SRF pathway, and this tubular epithelial cell-derived CTGF in turn induces fibroblast proliferation and Œ±SMA expression