Mechanistic target of rapamycin (mTOR) is regulated by metabolic cues, primarily glucose and amino acids, as well as by growth factors, hormones and cytokines
Mechanistic target of rapamycin (mTOR) is a sensor of metabolic stress and integrator of environmental cues
Representation of the mechanisms of UV-induced cellular response in skin: 1) UV-radiation is absorbed by the genomic DNA and causes direct DNA damage through the formation of CPDs and (6‚Äì4) PPs
Melanocortins such as Œ±-MSH and ACTH, produced in the pituitary and the epidermis, act as high-affinity agonistic ligands to the MC1R, a Gs-protein coupled receptor on the surface of melanocytes
UV photodamage is repaired by the nucleotide excision repair genome maintenance pathway
In melanocytes, enhancement of nucleotide excision repair by cAMP is dependent on a post-translational modification of ATR
Upon stimulation with an agonist such as CRP which induces GPVI-mediated signaling, DREAM binds to PI3K class Iβ (PI3K-Iβ) and facilitates the signal transduction pathway, thereby enhancing granule secretion and cytosolic Ca2+ levels
Ingenuity®Pathway Analysis (IPA®) revealed significant overlap between the XDP signature and gene networks related to (A) RNA polymerase II (p = 1.19 × 10−6) and (B) NFκB (p = 1.36 × 10−12).
The percentages of tumors with transposon insertions in genes for various signaling pathways identified by TAPDANCE analysis are indicated
[a | NO-mediated mechanisms of tumour cell killing by tumour-associated macrophages
After synthesis, histones H3–H4 and H2A–H2B engage with multiple different chaperones and enzymes on their way to chromatin
Regulation of hepcidin expression in hepatocytes in response to iron status and requirements (left) or inflammation (right)
A) Bar graph showing the average fold change in... B) Gene networks were generated using Ingenuity... C) The top 5 upstream regulators were determine...
Removal of the survival agent, NGF, inhibits the PI3K-AKT pathway
Utilizing a combination of immunoprecipitation (IP) and tandem mass spectrometry (MS) protein identification (ID), complemented by gene expression analysis, a comprehensive Ang-(1-7) stimulated Mas1 receptor signaling pathway was generated
p53 is activated in response to type I IFN signalling due to the presence of IFN-stimulated response elements (ISRE) within the p53 promoter sequence
ATM is activated in response to DSBs and repairs damaged DNA through homologous recombination (HR)
ATR is activated in response to single-stranded DNA generated by replication stress (stalled replication forks) or resected DSBs
HPV E6 and E7 interacts with core components of the interferon pathway
(A) SMN involvement in regulation of actin dyna... (B) SMN regulates the activation of c-Jun NH2-T... (C) SMN binds to and can regulate the level of...
A) Alternative splicing (AS) regulates metabolic activity through the pr... B) hnRNP K binds to the exonic splicing suppressor (ESS) in exon 12 of G...
(Left) Apoptosis can be triggered via intrinsic or extrinsic pathways, including by natural killer (NK) cells and cytotoxic T lymphocyte (CTL) granzymes
Cell death pathways can interact with each other, with the caveat that once a cell death pathway runs to completion, the interaction ends
The expression of Sost/sclerostin is tightly regulated by complex mechanisms involving crosstalk between systemic hormones, cytokines and mechanical stimuli (black lines)
Schematic diagram demonstrating the mechanism of action of perlecan and endorepellin in angiogenesis and autophagy
In cells infected by JEV, SeV or treated with 5’pppRNA, RIG-I signaling is strongly activated; through the NF-κB and IRF3 cascades this pathway induces the production of IFNα/β and proinflammatory cytokines such as TNFα through an autocrine/paracrine manner that synergistically upregulates STING expression
Both nutrient availability and metabolic network configuration affect how cells use metabolism to produce ATP, generate macromolecules, and regulate redox state
Model of pro- and antiapoptotic signaling from flagellin/TLR5
Diets high in specific dietary fats induce an inflammatory environment in the intestine that promotes intestinal tumorigenesis in genetically susceptible APCmin/+mice, independent of obesity and related metabolic conditions
Purine metabolism consists of a de novo synthesis pathway (red arrows) and a salvage pathway (green arrows) for purine bases
Model of STAT3-dependent negative regulation of DCs induced by HDAC inhibition
Schematic illustration of the dendrimer-based nanoplatform for targeted delivery of DJ-1 siRNA to the ovarian cancer cells via LHRH receptor-mediated endocytosis and the role of siRNA-induced suppression of DJ-1 protein in the combinatorial treatment
Schematic illustration of the role of Rho GTPase/Rho kinase signaling pathway in regulation of actin cytoskeletal organization and cellular processes in smooth muscle and non-smooth muscle cells
After DNA is damaged by cisplatin, and intrastrand crosslink is formed
(A) A volcano plot of the log2 ratio of the averages of Her2 positive ce... (B) Ingenuity pathway analysis suggested the ErbB signaling pathway was...
The involvement of GSK3 in TLR4 signaling pathways.Activation of TLR4 by LPS or alarmins (called ligand in the figure) involves dimers of TLR4 binding to CD14 and MD-2
Role of the ubiquitin–proteasome pathway in long-term facilitation in Aplysia
Genes that are mutated in chronic lymphocytic leukaemia (CLL) are involved in several cellular pathways (blue boxes)
AREs and GREs in growth factor signaling.A.
Mechanisms by which mild mitochondrial uncoupling protects neurons against oxidative stress, excitotoxicity and the accumulation of disease-related self-aggregating proteins such as amyloid β-peptide, Tau and Œ±-synuclein
Schematic representation of the signaling pathways involved in the migration induced by G-CSF in human trophoblast Swan 71 cells
Here is a signaling pathway map that represents how external cues regulate cytoskeleton dynamics, and further induce directional cell migration via these downstream signaling molecules
a | The role of autophagy in the elimination of microorganisms is shown
(A) After dimerization of a NOTCH receptor with a DLL/JAG ligand (a), proteolytic cleavage of NOTCH by ADAM family proteases and the γ-secretase complex occurs (b), releasing NOTCH intracellular domain (NICD) that translocates to the nucleus, interacts with the MAML/CSL complex to induce the transcription of target genes (c; HES, HEY family)
Schematic diagram shows projections of midbrain dopaminergic projections (ventral tegmental area or substantia nigra) to the frontal cortex and striatum and intracellular signaling pathway in a D1 receptor synapse
PDGFC gene expression in the signaling cell is regulated by the Egr-1 and Sp1 transcription factors
A. A simplified overview of the mitophagy pathway.
Signaling pathways triggered by GDNF activation of the RET transmembrane receptor
Basic components of the NOTCH signaling pathway
Several examples have been reported in which autophagy regulates cytokine production, or is subject to regulation by cytokines
One-carbon metabolism is encompassed of a complex metabolic network centered by the folate and methionine cycles
a: Entry into the cell cycle is typically induced in response to mitogenic signals that activate signalling pathways such as the RAS pathway
Major pattern recognition receptors (PRRs) that sense RNA and DNA virus pathogen associated molecular patterns (PAMPs) in the cytosol
Constitutive low levels of IFN-β that are produced by most cell types “prime” type I IFNs producing cells for a robust type I IFNs production upon sensing “danger” signals such as cytosolic DNA and TLR ligands
Role of Aim2 protein in non lupus-prone and lupus-prone strains of mice in the regulation of type I IFNs production
Following infection, replicating coxsackievirus subtype B (CVB) produce cytosolic double-stranded RNA (dsRNA), a nonphysiological form of mRNA recognized by the cytoplasmic receptor MDA5
Summary of identified microRNAs that target key proteins of autophagic pathway for regulation of autophagy
Schematic of junctional complex in the paracellular pathway of the BBB
The yeast mitogen-activated protein kinase signaling pathway, illustrating the signaling paths in responses to different signals
Examples of Metabolic Pathway Linking Gut Microbiota to Cardiovascular Diseases
The absence of cellular inhibitor of apoptosis proteins (c-IAPs) results in the activation of cell death pathways
The interplay between immune checkpoint proteins and cellular metabolism
Overview of the intrinsic and extrinsic apoptotic pathways, the TRADD/NF-Œ∫B survival pathway, and the growth factor (GF) receptors PI3K/AKT pro-survival signaling axis in CSCs
ABCA1, a major transporter that regulates HDL biogenesis and cholesterol efflux in macrophages accumulated in the artery wall, is regulated by a number of miRNAs including miR-33
Approximately 90pct of patients with MDS will have at least one mutation in one of the genes involved in DNA methylation, RNA splicing, chromatin modification, or in the other category
Formation of TF-FVIIa complex (on TF-containing MP) triggers thrombin generation via the extrinsic coagulation pathway and PAR-2 signaling in EOC cells
A sample result following Ingenuity Pathway Analysis with microarray data mapped onto known pathways for rapid interpretation of the biological significance of experimental data
Aurora A kinase, JAK-STAT and RhoA/ROCK pathway are important pathways regulating the proliferation, surivival, differentiation, enomitosis and proplatelet formation of megakaryocytes
Autophagy is a catabolic process in which excessive or damaged proteins and cellular organelles are degraded in autophagosomes
A schematic diagram showing the neuroprotective effect of celastrol on Cd-induced apoptosis in neuronal cells
The Canonical and Noncanonical Inflammasome
In order for the TCA cycle to function properly, it must be supplied with intermediate metabolites to ensure continuation of its reactions, a process known as anaplerosis
Impact of CTLA-4 Ig versus anti-CD28 domain Abs on alloreactive T cell responses
(a) Mechanical regulation of the Hippo pathway. Hippo is regulated by mu... (b) Crosstalk between YAP/TAZ and TGF-β, and between YAP/TAZ and Wnt. TG...
Induction of glycolytic and tricarboxylic acid cycle enzymes by M-CSF and GM-CSF
TLRs signaling pathway showed on TLR2 example
The TRL2 pathway is activated by Tollip and results in IRAK suppression
Chemotherapy induces damages in chromosomal DNA in cancer cells
(A) Use of a genome-scale integrated analysis o... (B) BJAB WT and LEXR samples (C) MDA-231 SENS and TRAILR samples after treat...
Wnt signaling through Frizzled (Fz) and Lrp5/6 activates mTORC1 in a PI3K-Akt dependent manner; mTORC1 increases the protein abundance of glutaminase (Gls) and stimulates glutamine oxidation for ATP production
TNF ligation with the TNFR1 receptor induces pro-caspase-8 recruitment to the activated TNFR1 signaling complex-I via FADD
The canonical and non-canonical NF-Œ∫B pathways
The activation modes of NF-Œ∫B in the pathogenesis of B cell lymphoma
The apoptotic pathways of NF-Œ∫B: TRAIL mediating the extrinsic pathway and p53 mediating the intrinsic pathway
Therapeutic targets in B cell lymphoma of NF-Œ∫B activation
Normally, as part of the down-regulation of the immune response, activated B and T lymphocytes up-regulate FAS and activated T lymphocytes up-regulate FAS-ligand
(A) Epigenetic regulation of IL-15 transcription by Zeb1 in normal and m... (B) Autocrine IL-15 production and consequent signaling in CD4+ T cells...
Lipid Kinase Activity: PI3Ks are classically well known for this lipid kinase activity
The network diagrams were generated using ToppCluster (www.toppcluster.cchmc.org) software.
Key players of the pathway are shown in blue, whereas the positive modulators are shown in yellow and the negative modulators in purple
Signaling networks activating the canonical RAF-MEK-ERK signaling pathway and that have been involved in SCLC metastasis (see text)
(Left) Symbiosis: A symbiotic gut microbiota operates under a functional intestinal epithelial cell (IEC) barrier, with steady state proportions of mucus, pattern recognition receptors (PRRs), antimicrobial peptides, and secretory IgA, which in turn contain the microbiota in the intestinal lumen
The central BCR signaling network constructed from literature
Simplified summary of mutated and/or dysregulated genes in human and mouse osteosarcoma (OS) that participate in the mTROC1 signaling pathway
Naïve CD4 T cells differentiate into IL-17 producing T cells under the cytokine environment including TGF-β, IL-6, IL-1β and IL-23
Intrinsic and extrinsic signals received by the upstream control sequences 1 through 4 (UCS1-4) of the IME1 regulatory region
During infection Lm- derived CDNs (c-di-AMP) are recognized by the host cell cytosolic pathway by binding to BTK-activated DDX41, which in turn recruits STING
Cartoon showing the multiple inputs regulating the function of a conventional PKC
An overview of the cell cycle phases and two examples of independent core pathways in the G1 stage
A cartoon illustrating two independent parallel pathways in the post-mitosis G1 phase (G1-pm) in cell proliferation: MAPK and the Hippo pathways
Simplified version of the complement cascade showing initiation on foreign/altered surfaces via the classical (CP), lectin (LP) and alternative (AP) pathways, generation of AP and CP/LP C3 convertases, amplification via the AP, and effector generation mainly via the AP and the terminal pathway
Proposed model for FoxO1 and AMPK regulation of EtOH-induced autophagy
Motifolio PPT Drawing Toolkit and the PyMOL Molecular Graphics System, Version 1.8 Schrödinger, LLC were used for designing the figure.
Upon NMDA receptor activation, the Ca2+/Calmodulin complex activates the βCAMKK/Œ±CaMKI pathway that in turn phosphorylates βPIX resulting in Rac activation and spine morphogenesis
Schematic illustrating our strategy to generate iPSCs resistant to IL-1-mediated signaling for tissue engineering applications
By binding anandamide (AEA) and 2-arachidonoylglycerol (2-AG), FABP1 may influence key aspects of the hepatic endocannabinoid system: A)
A). FABP1, not detectable in brain, binds and enhances uptake of arachidonic acid (ARA) translocated by fatty acid translocase protein (FATP) in the plasma membrane in cultured cells and likely also in hepatocytes.
GSK-3β modulation of LKB1-AMPK pathway in autophagy induction
Extrinsic cues can be divided into three general categories
(A) In hiPSC-CMs, receptor tyrosine kinases VEGFR2, PDGFRŒ±, INSR, and I... (B) Our results suggest that VEGFR2/PDGFR-inhibiting TKIs upregulate INS...
Schematic of PACAP/PAC1 receptor signaling to ERK activation
Top illustration shows disruptions in normal cell survival and normal apoptosis in glioblastoma
(a) Cortisol, when applied topically, produced endogenously, or derived... (b) In keratinocytes, GC were shown to activate the classic nuclear (GR)...
IL-1R8 inhibits IL-1R1, IL-18 and IL-33 signaling by competing with MyD88 and IRAK recruitment at the TIR domain, thus dampening the signaling pathway leading to NF-kB activation
Model of the putative role of central insulin resistance in attenuating leptin modulation of rHypoE-19 hypothalamic neurons
A network pathway was generated after uploading the PCR array data to the IPA software
LPS from Gram-negative bacteria is recognized by TLR4, inducing TRIF-dependent type I IFN production
Working model of TGFβ and NFŒ∫B pathway interactions that regulate GCT viability
Signaling mechanisms for PGF2Œ± and AL-8810 stimulation of FP receptor
A shared coregulator GRIP1 in the GR and type I IFN signaling networks
Model for genomic and nongenomic cross talk of the GnRHR and GR signaling pathways on the GnRHR promoter in LβT2 cells
Proposed Model for the Intracellular Mechanism of CART Action in Bovine GCsFSH stimulates Erk1/2 and Akt activation whereas CART treatment accelerates the termination of FSH-induced Erk1/2 and Akt signaling
A Possible Signaling Pathway that Mediates FSH-Induced Meiotic Resumption of Mouse OocytesAfter binding with its membrane-integrated receptor in cumulus cells, FSH uses PKAII as a downstream mediator after a transient increase of cAMP
Potential Signaling Pathways for Permitting Cross Talk between WNT and GnRHThe shaded pathway represents the skeletal features of the canonical Wnt/β-catenin signal transduction pathway
MiR gene expression is regulated in ways similar to protein coding genes
Ingenuity Pathway Analysis network showing the relationships between several assayed genes (emphasized with black arrows)
The mTOR protein exists in two structurally and functionally distinct complexes; mTOR complex 1 (mTORC1) contains the mTOR kinase, mLST8, RAPTOR and the inhibitory PRAS40 whereas mTOR complex 2 (mTORC2) contains mTOR, mLST8, RICTOR, mSIN1, and PROTOR
The various roles of C3 in complement activation and effector functions
In the primed nociceptor, neuroplasticity manifests as a PKCŒµ-dependent mechanical hyperalgesia , , ,
Glutamine/glutamate utilization in proliferating cells
Serine/glycine metabolism in proliferating cells
The role of adiponectin in lean and obese women to modulate fetal growth
The HGF/c-Met cell survival pathway is activated by matriptase, hepsin, and TMPRSS2
A microarray profiling of 467 human GBMs discovered that polo-like kinase 1 (PLK1) was highly expressed in these tumors and that it clustered with the proliferative subtype
The role of nitric oxide (NO) as a mediator of cancer phenotype has led researchers to investigate strategies for manipulating in vivo production and exogenous delivery of this molecule for therapeutic gain
BCR-mediated PI3K-driven molecular pathway plot was generated, in which arrows indicate phosphorylation and dotted arrows indicate interaction through the PH domain
Three significant signalling pathways were identified by the ingenuity pathway analysis tool (www.ingenuity.com) using up-regulated genes in paediatric Burkitt lymphoma samples in Toll-like receptors (TLRs), Mitogen-activated protein kinase (MAPK) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways.A, activation; E, expression; I, inhibition; L, proteolysis; LO, localisation; M, biochemical modification; P, phosphorylation/dephosphorylation; PP, Protein-protein binding; RB, regulation of binding; TR, translocation.
Cell–cell communication and cyclic AMP coordinates oocyte meiotic maturation in worms and mammals
A) IPA analysis suggests the involvement of signaling by ITAMs (immunore... B) Fold changes for individual genes showing significant alterations spe...
Ischemia leads to inflammation, tissue injury, and ROS production, which, when coupled with reperfusion can lead to injury
Mechanism of resistance and SCC development
Bile duct obstruction (BDO) induces inflammation and CBAs, mainly TCA, in the liver
(A) Strategy for ident... (B) obligate heterodimers (C) members of complex... (D) components of the... (E) enzymes catalyzing... (F) negative regulator...
The main pathways altered in GEMMs of cutaneous melanoma
The sun‚Äôs ultraviolet light damages DNA in cells in the skin, particularly keratinocytes and melanocytes
When MITF is induced (see ), it causes up-regulation of many genes relevant for pigmentation and cell survival
AMPK activation stimulates NO synthesis via multiple mechanisms: (i) phosphorylation of eNOS at Ser633 and Ser1177; (ii) increasing Hsp90 association with eNOS; (iii) increasing BH4 concentrations via GTP cyclohydrolase I (GTPCH1); (iv) reducing superoxide synthesis via inhibition of Nox and increasing antioxidant protein (superoxide dismutase (SOD), thioredoxin and catalase) levels
Physiological activators of AMPK in ECs include hypoxia/ischemia, shear stress, adiponectin, thrombin, bradykinin and VEGF (synthesis of which is stimulated by AMPK in other tissues)
EGFR stimulation induces activation of phosphatase SHP2 which decreases phosphorylation of STAT1 and subsequently expression of HLA class I and APM components
IGF-1 is significantly upregulated in TAMs in response to long-term CSF-1R inhibition in GBM
Anoikis signaling pathway in cancer cells
Schema of proposed clodronate signaling pathway
a | Interferon-γ (IFNγ)-mediated induction of macrophage activation coordinates the initial inflammatory response and the regulation of muscle differentiation
Clostridium difficile elicits the innate immune response via at least four different effectors, leading to the induction of proinflammatory cytokines and chemokines via nuclear factor-Œ∫B (NF-Œ∫B) and transcription factor AP-1
The myelin-associated inhibitors, such as Nogo, and scar-rich CSPGs activate intracellular RhoA to collapse axon growth cones
Bone morphogenetic protein 6 (BMP6) is produced by non-parenchymal cells in the liver in response to iron stores and flux
ECM–cell communication is dictated by focal-adhesion players
The major source of cellular ROS is the mitochondria
Metabolic shifts in hypoxia: the role of Hif1 and miR-210 in reductive stress
“Tissue Development, Cardiovascular System Development and Function, Organismal Development.” This was the top most associated network according to IPA core analysis of the TM gene input set which included the microarray study by Fan et al
Melanocyte activation integrated in the schematic view of the UV-induced pigmentation pathway in the normal skin
Autophagy is initiated upon activation of the AMPK signaling pathway
PDAC comprises of complex interactions between T cells, B cells, APCs, pancreatic tumor cells, and stromal elements
Cholesterol and isoprenoid synthesis pathway which shows the inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase by statins
NAD+ biosynthesis is mediated by multiple enzymatic reactions
Overview of the tuberous sclerosis complex and mTOR pathway
Many cellular stress stimuli activate p38MAPK leading to phosphorylation of specific serine residues in the cytoplasmic domain of EGFR (, , ) [Step 1]
Two bile acid synthesis pathways exist in the liver
Schematic representation of canonical cannabinoid receptor (CBR)-mediated, G protein-dependent signaling pathways
Based on GeneCodis3 analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, 23 significantly enriched pathways were revealed
Pathway alterations diagram integrating gene mutations and copy number alterations to identify pathways altered in UC- and CD-associated CAC
Desensitization of nAChRs during gestational nicotine/SS-exposure affects HIF-1Œ± levels increasing apoptosis and decreasing angiogenesis in the lung
Oxysterols are important regulators of many biological processes in the cell
mTOR mediates a number of developmental processes including neurogenesis and cellular proliferation and migration
A conserved insulin-signaling pathway in the ovary
CDK cyclin-dependent kinase, E2F E2 transcription factor, ER estrogen receptor, GRB2 growth factor receptor-bound protein 2, HR+ hormone receptor-positive, mTOR mammalian target of rapamycin, PI3K phosphatidylinositol 3-kinase, Rb retinoblastoma, RTK receptor tyrosine kinase, S6K S6 kinase
Summary of ergot-alkaloid biosynthetic pathways with emphasis on Clavicipitaceae
As shown in , activation of the β2AR induces bronchorelaxation (i.e.
Macrophage-centered therapeutic approaches are aimed either at activating their antitumor activity (Panel A) or inhibiting their recruitment and functions related to tumor promotion (panel B).Panel A: the concerted action of microbial moieties (acting via TLRs) and IFNγ induces M1-like functional polarization and can activate macrophage killing of tumor cells; macrophage-mediated antibody-dependent cytotoxicity (ADCC) can mediate the therapeutic effect of therapeutic antibodies; interference with the SIRPŒ±-CD47 pathway activates macrophage-mediated antibody-dependent phagocytosis (ADCP) and results in functional skewing of macrophages in an M1 direction and antitumor activity; an anti-CD40 antibody re-educates M2-like macrophages in the tumor microenvironment, leading to re-establishment of tumor immune surveillance.Panel B: Inhibition of monocyte-attracting molecules, including chemokines (e.g CCL2, CCL5), VEGF, CSF-1 and complement mediators (C5a) with specific monoclonal antibodies (e.g.
mTOR pathway integrates signals from growth factors and nutrients to regulate diverse cellular processes, including translation, autophagyand transcription of genes involved in ribosome biogenesis and metabolism
A large number of miRNAs display tumor suppressive activity by directly targeting mTOR and/or upstream positive regulators of mTOR
Many oncogenic miRNAs are overexpressed in human cancers that promote the development and/or progression of tumors by stimulating mTOR signaling through down-regulation of negative regulators of mTOR
mTOR broadly regulates miRNA biogenesis in mammals through Mdm2-dependent ubiquitination and degradation of Dorsa
Binding of the BMP ligand dimer to its type I and type II receptors forms the BMP transmembrane signalling complex
It is believed that the rapid increase of synaptogenesis, by modulating prefrontal and hippocampal glutamatergic synapses, is a convergent mechanistic pathway underlying the beneficial behavioral effects of RAADs
TNF receptor superfamily (TNFRSF) proteins recruit one or several adaptor proteins (TNFR associated factors 1 to 6 (TRAFs), TNFR associated death domain protein (TRADD) and Fas associated death domain protein (FADD)) after ligand binding
Genetic alterations of key components of the growth factor receptor-PI3K-Akt signaling pathway are frequently observed in primary (IDH wild-type) GBM, which eventually activate mTOR signaling
Mutations in the cardinal genes for gliomagenesis including IDH and RTK pathway components are the central force to drive metabolic reprogramming in gliomas
ROS are associated with the generation of CIN
(A) CSL (green) interacts with NIC... (B) in the absence of NICD, the sh... (C) If CKII activity is low or abs... (D) in cells lacking NICD and cont...
UVB stimulates the production of PAF and ox-GPCs via reactive oxygen species, which then act upon the keratinocyte PAF-R resulting in MVP formation and release
Cyclin D/Cdks are activated in response to mitogenic signals and initiate phosphorylation of Rb, a process that is completed by cyclin E - Cdk2
The solid lines represent the plasma membrane, and the discontinuous lines show the nuclear membrane
Interactions of IGF and ERβ signaling pathways in malignancy
Overlap of the present results with Greengard’s neurotransmission integration scheme
Comparison between SHH-treated CGNPs of indicated genotypes cultured for 24h with [1,6-13C] glucose, showing 13C labeling of ribose-labeled adenine nucleotides, and glutamate (mean±s.e.m).
Activation of type 2 histamine receptor (H2Rs) in parietal cells by histamine induces cAMP-dependent PKA activation
Schematic representation of proteins that interact directly or indirectly with mGlu1/5 receptors and mediate receptor signalling
TFH cell differentiation is initiated by activation of CD4 naïve T cells by dendritic cells in presence of IL6, IL21 and IL12 leading to STAT3/STAT4 activation
GTP-bound GNAQ directly activates PLC β, which generates the second messenger DAG
mTOR-signaling pathway: mTORC1 and mTORC2 complexes and the key signaling nodes that regulate mTORC1 and mTORC2
Effects of alterations in mTOR signaling pathway on spermatogenesis
Roles of mTOR signaling pathway in cancer in type 2 diabetes
Roles of Autophagy signaling pathway in cancer in type 2 diabetes
mTORC2 signaling is elevated in many cancers via two distinct mechanisms.In non-small cell lung cancer and melanoma, Rictor amplification drives mTORC2 signaling while mTORC2 signaling is hyper-activated by upstream growth factor signaling pathway mutations in prostate cancer, leukemia and GBM
KEGG MAPK signaling pathway (KEGG ID: hs04010)
Proposed mechanism for the action of 7,8-dihydroxyflavone (7,8-DHF) on enhancing the outcome of exercise post-TBI
(A) Molecular mechanisms of dietar... (B) Mechanism and proteins involve... (C) Mechanisms and proteins involv... (D) Mechanisms and proteins involv...
Gram-negative bacterial infections lead to the activation of TLR4-TRIF-type I IFN pathway, which induces the expression of caspase-11 and GBPs
Many signals converge on the NF-Œ∫B and STAT1 pathways to coordinately reprogram beta cells at a transcriptional level, leading to inflammation-based changes in insulin secretion, β-cell mass, or both
A Activation of immune cells results in substantial remodeling of epigenetic landscapes
Recognition of pathogen by immune cells initiates a genetic program that promotes use of numerous metabolic pathways for biogenesis (i.e.
During the early phase response, the Akt/mTOR complex 1 (mTORC1)/hypoxia inducible factor-1 (HIF-1α) pathway drives the induction of aerobic glycolysis by increasing the expression of glycolytic enzymes including lactate dehydrogenase (LDH), the M2 isoform of pyruvate kinase (PKM2) and pyruvate dehydrogenase kinase (PDHK)
During the early metabolic response to sepsis, tubular epithelial cells might undergo a metabolic switch from oxidative phospharylation (OXPHOS) to aerobic glycolysis via the Akt/mTOR complex 1 (mTORC1)/hypoxia inducible factor 1α (HIF-1α) pathway, resulting in an early anabolic, proinflammatory stage
Panel A shows cGMP-dependent and independent nitric oxide (NO) signaling pathways
A schematic overview of hippocampal signaling pathways whose modulation by sleep deprivation may contribute to effects on memory formation
Prorenin binding to PRR results in the generation of Angiotensin (Ang) peptides and the subsequent activation of angiotensin type 1 receptors (AT1R)
A proposed mechanistic model as to how ciRS-7 functions as a miR-7 sponge and regulates EGFR/RAF1/MAPK pathway via inhibiting miR-7 activity
Panel A shows that papillary thyroid carcinomas have mutually exclusive activating mutations in BRAF, RAS, and RTK
The frequency of the main somatic genetic defects in papillary, poorly differentiated, and anaplastic thyroid carcinoma is shown, based on the largest published series studied by next−generation sequencing., Because anaplastic thyroid carcinomas are extensively infiltrated by tumor−associated macrophages, deep sequencing is required to make reliable mutation calls.
The figure illustrates bipartite binding of SAP97 simultaneously to the ß1-AR PBM (via its second PDZ) and to AKAP5 (via the I3 domain of SAP97)
A, Organization of SNX27 into its three major protein binding domains
Cellular signaling pathways and transcriptional regulatory circuits mediating physiologic cardiac hypertrophic growth
A) Compared to chow-fed control (fl/fl) mice, hepatic insulin signaling... B) Proposed sequence leading to unique selective insulin resistance in H...
The Notch pathway has multiple roles during follicle assembly and growth, steroidogenesis, and ovarian vascular development
The three primary routes for activation of complement are: (1) the lectin pathway (LP), (2) the classical pathway (CP), and (3) the alternative pathway (AP)
Under basal conditions NRF2 is bound in the cytosol by interaction with KEAP1
Proteins containing cysteine residues with a free thiol group can be modified through oxidation, glutathionylation, nitrosation, sulfhydration or sulfenation to modulate protein function
The activation of the JAK2/STAT5 pathway promotes cell proliferation and survival through transcriptional upregulation of p85α (Pik3r1), p110α (Pik3ca), and Akt1 as well as through direct interaction of tyrosine phosphorylated STAT5 with the p85α regulatory subunit of PI3K
Compared with normal cells (left), the flux of glucose metabolism and glycolysis is accelerated in cancer cells (right) by preferential expression of transporters and enzyme isoforms that drive glucose flux forward and to adapt to the anabolic demands of cancer cells
Several oncoproteins (in blue boxes) are known to either elevate the expression or induce the activity of enzymes and transporters that facilitate a high rate of glucose metabolism in cancer cells
Differentiated hepatocytes use the reversal glucose transporter, GLUT2, for the uptake and export of glucose
The PI3K-AKT pathway from the KEGG mapper showing several upregulated proteins indicated in the pink based on the two fold change in the protein expression between LNCaP-95 androgen resistant and wildtype LNCaP prostate cancer cells (A)
Downregulation of several proteins in the oxidative phosphorylation pathway identified in the global proteomic data for LNCaP-95 androgen resistant prostate cancer cells
Estrogen synthesis and aromatase promoter II use in the ovary
Activation of aromatase promoter I.4 and promoters I.3/II in breast adipose fibroblasts and promoter I.7 in breast endothelial cells
CREB-induced IL-10 production is regulated by IFN-γ
In the canonical Wnt signaling pathway, Wnt ligands stimulate the activation of β-catenin to induce transcription of Wnt target genes via interaction with the Lef1 transcription factor promoter
Aging is a complicated process, often characterized by increased ROS and inflammation
a | Under homeostatic conditions, self-reactive B cells are subjected to both positive and negative selection mechanisms as they transit into the naive B cell pool and establish the naive repertoire
Key components of the stress response signaling network in C
PD-1 is also expressed on T-cells following TCR engagement and activation
Pathway analysis of gene expression data using Ingenuity online tools indicated activation of MYC, STAT3 and β-catenin (CTNNB1) transcription networks in both Tff1 KO mice gastric LGD and human gastric cancer samples
Damage to or high-threshold activation of first-order neurons by noxious stimuli induces the release of ATP, CC-chemokine ligand 2 (CCL2), CCL21 and neuregulin 1 (NRG1), as well as endogenous danger signals to initiate central immune signalling in the dorsal horn of the spinal cord
Left: Lipopolysaccharide (LPS) acts as a ligand and binding to Toll-Like Receptors (TLR)
Establishment and maintenance of both oncogene-induced senescence (OIS), and replicative senescence (RS) is dependent on DDR activation
During DNA replication, translation and transcription, as well as during epigenetic and post-translational modification, DNA is repaired using a number of pathways including HR, MMR, NER, BER, NHEJ, and TLS
Mechanistic association of insulin signaling with mitochondrial function in normal and diabetic brain
Following Caspase 3 (green) activation by initiator caspase proteins, Caspase 3 is inhibited by the binding of XIAP (gray)
Resident adult hepatic/stem cells are activated from their niche after receiving certain factors and signals or transitioned from hepatocytes or myofibroblasts by ductal metaplasia or MET (Left column); and proliferated (Central column); then differentiated towards hepatocytes by the activation of Wnt/β-catenin signaling and the up-regulation of Wnt2 and Wnt9b, differentiated towards cholangiocytes by the activation of Notch signaling pathway, trans-differentiated into hepatic stellate cells by the up-regulation of TGF-β and CTGF, trans-differentiated into myofibroblasts by the up-regulation of Fox1 and TGF-β and the activation of non-canonial Wnt signaling pathway, and transformed into tumor-initiating cells by the up-regulation of TGF-β and Bmil and the activation of Wnt/β-catenin signaling pathway (Right column)
LTA derived from the commensal microbiome on the skin surface increases the expression of cathelicidins in MC granules via induction of Cnlp
a | The resting vascular endothelium in its natural anticoagulant state
Shh pathway targets and regulatory networks
Systematic analysis of genes in pathways upstream of the nuclear factor-Œ∫B (NF-Œ∫B) complex revealed a large repertoire of diffuse large B cell lymphoma (DLBCL)-specific genetic alterations in B cell receptor (BCR) and myeloid differentiation primary response 88 (MYD88) pathways
For the interaction between the Wnt/β-catenin and TGF-β pathways, the responsive Smads (Smads 2 and 3) can directly associate with lymphoid enhancer binding factor 1/T cell-specific factor (LEF1/TCF) to synergistically activate target genes [,]; the tumor suppressor Smad4 is negatively regulated by Wnt/GSK3 phosphorylations []; Axin, a core component of the β-catenin destruction complex, may function as an adapter, facilitating Smad3 association with the receptor complex thereby promoting TGF-β signaling []; FOXQ1, a member of the forkhead transcription factor family, can be induced by TGF-β1 and enhance the nuclear translocation of β-catenin []
Nonproliferating cells are capable of removing ICLs in a manner that is independent of DNA replication
(A) Venn diagram showing significa... (B) Gene ontology analysis using D... (C) A large TGF-β network (P < 1.0... (D) JQ1 suppressed genes enriched...
In KRAS mutant NSCLC, acquired resistance to ganetespib is initiated by hyperactivation of ERK, which in turn augments the expression of master switch, p90RSK
Eph and Notch receptors are asymmetrically distributed from their ligands at cell-cell contacts
Cascade A represents SK-MEL-28 cellular response to BRAF V600E inhibitors (BRAFi) within the BRAF V600E mutation
In response to growth signals, mTORC1 activation leads to S6K1 mediated-phosphorylation of CAD, the rate-limiting enzyme of the de novo pyrimidine synthesis pathway, thereby acutely stimulating an increase in pyrimidine synthesis
Glucose is oxidized to pyruvate (glycolysis)
Hyperglycemia, possibly along with IR (diabetes pathology) may initiate the apoptotic pathway, including caspase activation, and tau cleavage
(A) In the canonical pathway, a st... (B) In WT cells, PSMA expression d... (C) Bypassing PSMA interference by... (D) The absence of PSMA allows sta...
Autophagy (or macroautophagy) is a catabolic process in which double membrane vesicles called autophagosomes sequester and degrade organelles, proteins, and other cytoplasmic constituents in response to cellular stress
A. Schematic of the TSC complex components, their regions of association (dashed lines), and Akt phosphorylation sites on TSC2.
A. Several points of cross-regulation exist between the PI3K-Akt pathway and both the RAS-ERK and AMPK pathways, leading to both reciprocal pathway regulation and convergent regulation of downstream processes.
A proposed model for I-SMAD-regulated signaling that enhances HSPG expression, cholesterol uptake and HCV entry
Schematic diagram depicting the signalling pathways linking insulin-RBM20-titin splicing
Schematic representation of the PI3K-AKT-mTOR signaling pathway
(A) Network-based cluster analysis of RPL10A/uL... (B) Network-based cluster analysis of RPS25/eS2... (C) Almost every component involved in the tran...
In addition to activating its downstream transcription factors such as signal transducer and activator of transcription factors (STATs) the receptor-associated Janus kinase 2 (JAK2) can also affect chromatin structure via direct and indirect mechanisms
Three distinct mechanisms contribute to the EGFR-mediated radioresistance in cancer cells (a) In response t... (b) As a conseque... (c) The phosphory...
Using multiple mechanisms, PI3K/AKT pathway activation primes chromatin for subsequent transcriptional activation
PI3K/AKT pathway hyperactivation represents a viable therapeutic modality in cancer
PLC-γ1 deficiency perturbs phosphorylation on canonical TCR signaling proteins
MLK3 mediates CXCL10 induction during hepatocyte lipotoxicity by triggering a MAPK signaling pathway that induces the activating phosphorylation of MKK3/6, p38 resulting in STAT1 phosphorylation at Ser727, and its nuclear localization
A simplified view of canonical Wnt signaling: Cytoplasmic β-catenin (βcat), when not bound to E-cadherin at the cell membrane, is phosphorylated by GSK-3 in complex with the proteins adenomatous polyposis coli (APC) and Axin
TGF-β family member signaling and its target in CRC
The SPPS-based strategy for GBAP synthesis
Proposed model of the Src/IGF-IR signaling axis present in both prostate cancer Exo and cells
In the presence of sufficient amino acids, mTORC1 is recruited to the lysosome and activated through the actions of the Rag GTPases, the Ragulator complex, and the V-ATPase
LPS binding to TLR-4 initiates Src activation which subsequently leads to induction of p-65, NF-Œ∫B, STAT1 and cofilin
RIG-I and MDA5 bind distinct moieties on non-self RNAs, which triggers post-translational modifications, oligomerization (not depicted in this schematic), and translocation to mitochondria and mitochondrial-associated membranes (not depicted)
Negative regulators act at multiple points along the RLR signaling pathway to inhibit activation of RIG-I and MDA5, or to prevent their interaction with MAVS
Additional negative regulators prevent or diminish the activity of MAVS, which blocks downstream formation of the signaling synapse and transcription factors
Glycolysis and the PPP provide biosynthetic intermediates and reducing power for cell growth and proliferation
(A) M1 macrophages, effector T cells and cancer cells are characterized... (B) Activation of growth factor receptors leads to Akt-mediated upregula...
aAbbreviations: A, adenylation; ACP, acyl carrier protein; KS, ketosynthase; OAS, Œ±-oxamine synthase; OMT, O-methyltransferase; PCP, peptidyl carrier protein; PPTase, phosphopantetheinyl transferase
aAbbreviations: A, adenylation; ACP, acyl carrier protein; AT, acyltransferase; DH, dehydratase; ER, enoyl reductase; KS, ketosynthase; KR, ketoreductase; OAS, α-oxoamine synthase; OR, oxidoreductase; TE, thioesterase
Genes highlighted in pink are frequently deleted in human cancers and RASopathies, as described in the text
2.1. BDNF released by glial cells (and activation of the tropomyosin receptor kinase B [TrkB]) has protective effects in dopaminergic cells that can potentially be associated with the regulation of neuronal bioenergetics.
Insulin-induced PI3K-Akt and MAPK network in hepatocytes
Model depicting the Cdc42-mediated regulation of EGF receptor interactions with c-Cbl
Schematic representation of the main cellular mechanisms of chemioresistance
Schematics illustrating key features of SHP2 regulation and function
Antigen binding and aggregation of the B cell receptor (BCR) combined with co-receptor ligation leads to activation of the Ras/Raf/Mek/Erk and PI3 kinase/Akt protein kinase cascades, which have been shown to activate mTORC1 (mTOR/Raptor complex) activation through phosphorylation and inhibition of TSC2 (tuberous sclerosis complex protein 2)
Model for the role of mTORC1 signaling in suppression of lipolysis in adipocytes
To identify coherent networks of genes influenced directly by smoking, we examined the potential interconnections of the 310 genes identified in the genome wide methylation analysis using PPI information in the STRING database
Induction of oxidative pathway response during alcohol metabolism
Pathogen-containing vacuoles (PVs) are marked by Ub, galectins (Gals), autophagy adaptors (e.g.
Compared to normal tissue, alternative splicing of the FGFR gene can switch expression of FGFR from the IIIb isoform to the ligand promiscuous IIIc isoforms
Amino acid limitation causes a decrease in mTOR signaling which leads primarily to an increase in IGFBP-1 secretion
Cytosolic sensing of double stranded DNA (dsDNA) by cyclic GMP-AMP synthase (cGAS) leads to the production of cyclic GMP-AMP (cGAMP) as a second messenger, which then activates the stimulator of interferon genes (STING) in the endoplasmic reticulum (ER) and further upregulates type I interferon (IFN) transcription via the recruitment of TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3)
Schematic illustration of up and down-regulated metabolic proteins in PANC-1 cells
It is not clear whether BER and TOP1-mediated SSBs actually require a sensing step; however, direct breaks are detected by polyADP ribose polymerase 1 (PARP1)
IRE1Œ± arm of the unfolded protein response
Insulin signaling pathways are initiated by insulin binding to the extracellular alpha subunit of the insulin receptor (IR), followed by a conformational change in the beta subunit of the IR, which has intrinsic tyrosine kinase activity
Schematic diagram of antiviral mechanisms in mammalian cells: IFN-based antiviral system, including IFN expression pathway (AE) and IFN response pathway (AR); the intrinsic antiviral pathway (B); and the RNAi antiviral pathway (C)
miRNA pathways in myeloid differentiation and myeloid-derived malignancies
miRNA pathways in mature immune cell function
Mechanisms of action of PD-1 and CTLA-4 pathway inhibitors
mTORC1 has six and mTORC2 has seven protein components
Growth factors such as insulin activate mTORC1 through the PI3K-Akt pathway
S6K1 acts as a negative regulator of mTORC1 activity by creating negative feedback loops
Schematic representation of Dox- and AD198-induced apoptosis and chemosensitization by inhibition of the PI3K/AKT pathway with LY294002 in OSCCs in vitro
Hypercalcuric hypomagnesemias such as FHHNC, ADH, and BS affect the TAL by disturbing the lumen-positive potential
Overview of innate immune cells and their functions in the CNS
An overview of central carbon metabolism
AuxRE and GRE are the sites for recruiting these suppressor and activator complexes
During T-cell receptor (TCR) crosslinking with antigen presented by major histocompatibility complex class II (MHCII) molecules (in CD4+ T cells) or class I molecules (in CD8+ T cells), the tyrosines of the cytoplasmic tail of PD-1 become phosphorylated (P)
Ligation of PD-1 that is expressed in activated T cells by PD-L1 expressed on antigen-presenting cells, nonhematopoietic parenchymal cells, or tumors alters T-cell metabolic reprogramming by inhibiting glycolysis, amino acid metabolism, and mitochondrial metabolism and promoting the accumulation of polyunsaturated fatty acids (PUFA) and activation of fatty acid oxidation (Panel A)
When insulin enters the bloodstream and binds to its receptor, members of the insulin receptor substrate (IRS) family are activated
IFN signaling pathway is shown with green arrows
Schematic summary of the possible link between IGF-1R signaling, synaptic changes, neurotransmitter function and inflammatory response
Upon viral infection, RIG-I and MDA5 recognize cytoplasmic viral RNA species: short dsRNA containing a 5′ tri- or di-phosphate moiety by RIG-I and long dsRNA structures by MDA5
Models depicting the proposed functions of the FA protein interaction network in the repair of stalled or collapsed DNA replication forks
Post-translational Modifications (PTMs) that Modulate the Retinoic Acid-Inducible Gene I (RIG-I)-like receptor (RLR)–Mitochondrial Antiviral Signaling Protein (MAVS) Signaling Pathway
The endothelial cell Dll4-activated NOTCH signal pathway requires SUMOylation of N1ICD for NOTCH1 cleavage to occur, which releases N1ICD from the cell membrane, stabilizes N1ICD and initiates substantial co-transcriptional activity in the nucleus
Platelet 12-lipoxygenase (p12-LOX) generates 12(S)-hydroperoxy-8,10,14-eicosatrienoic acid (12(S)-HpETrE) from dihomo-γ-linolenic acid (DGLA; 8,11,14-eicosatrienoic acid), which is readily reduced to 12(S)-hydroxy-8-10-14-eicosatrienoic acid (12(S)-HETrE))
In the classical TGF-β1-SMAD-3 pathway, binding of ligands to constitutively active type II receptor phosphorylates the type I receptor, which in turn propagates the signal by phosphorylating the R-SMADs (SMAD-2 and SMAD-3)
(A) A simple regulatory network that controls stem cell self-renewal, pl... (B) Conserved Ras-ERK/MAPK signaling pathway in mammals and C. elegans....
(A) In flies, Ft binds to Ds, and the strength... (B) In flies, the Ft/Ds system is activated alo... (C) In vertebrates, the Ft ortholog Fat4 binds...
The formation of the Bu metabolites is depicted above
BCR–ABL pathway drives signaling in H929 cells and phosphorylation is inhibited by imatinib
Depicted in this diagram is a simplified overview of the metabolic pathways and factors discussed, as well as therapeutics that have been tested to reconfigure imbalances in lupus immune cell metabolism
A and B: Canonical (β-catenin-dependent) pathway
Substituting SNORD115 with an oligonucleotide
The processing and digestion of engulfed apoptotic cells utilizes LC3-associated phagocytosis and promotes an anti-inflammatory response
Differentially regulated genes are mapped onto the KEGG pathway (hsa04510), which is found to be enriched between the culture conditions
IFN-α stimulation in HUVECs leads to enhanced NF-kB signaling and upregulation of miR-155
Schematic of the STAT3 pathway and therapeutic targets
Schematic illustration of possible interactions between PVN inflammation and sympathoexcitation in spontaneously hypertensive rats
A. Schema depicting involvement of MUC1-C in activating the WNT/β-catenin pathway and thereby the induction of MYC, lenalidomide (LEN) resistance and CD44.
Summary diagram depicting the current understanding of GRK3 regulation and function in the cardiovascular and respiratory systems
PI3K pathway is activated in response to several extracellular stimuli resulting in the activation of downstream serine/threonine kinase, mTOR
Diagram of the PI3K/AKT/mTOR pathway and interaction with PTEN and TSC1/TSC2
(A) The MUST complex (MAGEL2-USP7-TRIM27) is important for the retromer-... (B) Molecular mechanism of how the MUST complex regulates WASH activity....
Dendritic cells (DC) can either activate adaptive immunity or tolerize T cells depending on their state of maturation
(A) Cones use glutamate (Glu) to signal cone bipolar cells (cBCs) and ho... (B) Model that accounts for how both the effectiveness of the GABA feedf...
Systemic lupus erythematosus (SLE)-activated platelets induce endothelial cell activation via an interleukin-1β (IL-1β) pathway
Schematic representation of the major pathways involved in excitation-contraction, and relaxation coupling in GI smooth muscle
(A) Hematopoietic stem cells (HSCs) exhibit condense and immature mitoch... (B) Mechanisms of metabolic regulation of HSC function. Under hypoxic co...
Schematic model of the preventive effect of rapamycin on hsBAFF-evoked B-cell proliferation and survival
Schematic diagram for molecular mechanisms of activation of ER stress
In hepatocytes, Cyp7a1 initiates bile acid synthesis from cholesterol to form cholic acid (CA) and chenodeoxycholic acid (CDCA) in human liver
AngII-activated AT1 receptor initiates classical second messenger-mediated signals such as Ca2+, elevation and PKC activation as well as PTK activation and ROS production via heterotrimeric G proteins, which then activate ADAM17 via phosphorylation
The AT1 receptor interacts with heterotrimeric G proteins and activates Rho/ROCK pathway via RhoGEF
Upon injury or infection arachidonic acid (AA) is released from membrane stores through the action of cytosolic phospholipase A2
Several small-molecule inhibitors targeting different nodes in this pathway are under development for the treatment of cancer
AMPK-activating drugs that reduce cellular ATP levels, such as the antidiabetic metformin, promote tumor suppressive actions in a LKB1-dependent manner
Synthesis and turnover of complex sphingolipids along with actin dynamics are regulated by PI4,5P2 and the Slm1 and Slm2 proteins
Multiple and bidirectional connections between actin dynamics and endocytosis
Transcriptional programs controlling endocytosis and genetic reprogramming by endocytosis
Endocytic circuitries in asymmetric cell division
Schematic view of the VEGFvascular endothelial growth factor pathway and the sites of action of its inhibitors
Diagram shows a simplified scheme of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTORmammalian target of rapamycin signaling pathway
oxPCCD36 accumulate in the circulation in hyperlipidemia, bind to platelet CD36 and induce formation of CD36/TLR2/TLR6 complex and activate downstream signaling via innate immune signaling cascade, TIRAP-MyD88-IRAK1/4-TRAF6, leading to platelet integrin Œ±IIbβ3 activation via the SFK-Syk-PLCg2 pathway
In the assembled B cell receptor (BCR), CD79A–CD79B is weakly bound by Src family kinases (SFKs)
A) The disease-state schematic depicts the contributing factors of diet-... B) The disease treatment/prevention pathway represents the role of FXR a...
Bacterial effector proteins from S. Typhimurium and S. flexneri and disruption of the cytoskeleton by cytochalasin D induce the NOD1/2 signaling pathway and this is dependent on the activation of small Rho GTPases.
Induction of ER stress with the chemical inducers DTT and Thapsigargin or infection with Brucella abortus induce the IRE1 pathway of the unfolded protein response, which leads to activation of NF-Œ∫B via a process dependent on TRAF2, NOD1/2 and RIP2
The decision to enter dauer begins with environmental components and proceeds through two parallel pathways before converging onto a lipid hormone signalling pathway
Upon recognition of viral RNA, RIG-I and MDA5 undergo a conformational change that triggers their interaction with the adaptor protein MAVS
Mammalian cells sense flavivirus infection mainly via cytoplasmic PRRs such as the RLRs and the DNA sensor cGAS, which in turn activate their adaptor proteins MAVS and STING, respectively
The combination of cross-linking antibodies specific for TNFRSF members and innate cytokines, such as IFN-1, driven by engagement of PRR, synergize to expand conventional effector T cells (Tcon)
Protein-bound uremic toxins could take use of five potential toxin-conjugated albumin-receptor pathways to either promote or suppress inflammation
Lens cell differentiation (light-moderate-dark blue contours) is illustrated at mouse embryonic stages E10.5, E11.5, E12.5, and E14.5.
(A) Schematic diagram of signaling pathways in the epithelial cells at t... (B) In differentiating fiber cells, FGF signaling through the Ras-MAPK p...
The crosstalk between Panx1 and ligand-gated receptor channels
Schematic representation of inhibition of exosome biogenesis and secretion by Manumycin A in CRPC cells
Transcriptional regulation of Th9 cell generation
Effective communication between cells is central to development, tissue and organism homeostasis, and host defense
Upon engagement by ligand, receptor-associated Janus Kinases (Jaks) become activated and phosphorylate both each other and the intracellular tail of their receptors, thereby creating docking sites for latent, cytoplasmic transcription factors termed signal transducers and activators of transcription (STATs)
The JAK-STAT Pathway: Impact on Human Disease and Therapeutic Intervention
Schematic representation of the role of the TGF-β-Smad and BMP-Smad signaling pathways in myocardial infarction and the mechanisms of some associated potential therapies
Mechanism of synergistic action of VCN-2 and docetaxel (DTL)
Stress causes activation of Ral to Ral GTP and the formation of LOOH from membrane lipids
For convenience, the PI 3-kinase activation is highlighted, as naïve & activated B cells are combined, along with helper T cells
The figure shows the activation of RAS initiated through interaction with phosphorylated RET
The figure shows a schematic representation of major regulators RB1-mediated cell cycle regulation
Model of the role of FAK in regulating lineage commitment, proliferation, and osteogenic differentiation of BMSCs
The core of the Hippo pathway is the kinase cascade of MST1 and MST2 and LATS1 and LATS2
The mammalian intestinal mucosa is to form villi and crypts
In normal homeostasis, the Hippo pathway is constitutively active to keep YAP1 activity at low levels
When the Hippo pathway is activated, cytoplasmic YAP1 inhibits Wnt signalling by sequestering β-catenin in the cytoplasm
Disruption of Hippo signalling by deleting core kinase components (MST1, MST2, SAV1, MOB1A, MOB1B, LATS1, LATS2 and Merlin) leads to uncontrolled proliferation of hepatocytes and bile duct epithelial cells (cholangiocytes)
Hypothetical roles of ANTXR1 as a modulator of HbF expression
Crystalline Silica (CS) promotes lung tumor progression through LTB4-BLT1 pathway
Immune cell function is a product of their metabolic state
a | In adipocytes, following binding of the steroid hormone oestradiol (E2), oestrogen receptor-Œ± (ERŒ±) engages in phosphorylation (P) of Ser (S) and Thr (T) residues in subunits of carbohydrate-responsive element-binding protein (ChREBP) ‚Äî a key transcription factor regulating the expression of genes involved in lipid biosynthesis
T Cell Signaling and Gene Regulation Defects in Systemic Lupus Erythematosus (SLE)
Immune and neuronal receptor signaling activate molecular pathways, which feed into the mTOR pathway and activate MEF2-dependent transcriptional regulation
Proper tuning of TCR activation is critical for the functional regulation of helper T-cells, including cytokine production, lymphocyte differentiation, clonal expansion, and cytotoxic effector functions
Accelerated lipolysis generates acetyl CoA from fatty acids due to impaired pyruvate dehydrogenase (PDH) by hypoxia inducible factor 1Œ± (HIF1Œ±) via pyruvate dehydrogenase kinase (PDK) and possibly directly by ammonia
(Apoptosis) SeV, VSV, EMCV, and AdV activate a RIG-I-dependent signaling cascade resulting in cleavage of caspase-3 and cell death
UL97 phosphorylates DREAM complex members (LIN52, p130, p107), Rb complex members (Rb, E2F3), and an MMB-interacting protein (FoxM1), each of which regulate transcription at different stages of the cell cycle
Prolactin and progesterone are important regulators of STAT proteins
A subset of dopamine neurons that innervate the mushroom body neurons promote forgetting
Pictorial representation of the signaling pathway activated by VLA-5 binding to fibronectin
Various secreted soluble factors from tumor cell stimulate microglia and astrocyte activation
PTEN controls the G2-M transition to prevent bypass of the G2 checkpoints and premature entry into mitosis (M)
Possible mechanisms of inhibition of receptor tyrosine kinases by EGCG
A. An increased expression of Dab2 was found in zona glomerulosa (ZG) and APA; whether it is due to reduced destruction of the Dab2/clathrin complex is unknown.
NO/H-NOX regulates Vf-HaHK and Sili-HaHK autophosphorylation activity and their symbiotic relationships with their respective eukaryotic hosts
(A) Schematic depicting the interiors of a cell in a pre-stretch conditi... (B) Schematic depicting activation of the integrin-mediated pathway, Rho...
Illustration of the action key POR3-differentially expressed genes in the cell survival network generated using Ingenuity®Pathway Analysis
The schematic portraits the components and major events of the extrinsic and mitochondrial apoptotic pathways
(a) Schematic representation of the mTOR signaling pathway before discov... (b) Simplified schematic representation of our current understanding of...
a | Musashi 2 (MSI2) protein inhibits NUMB translation by binding directly to the 3′-untranslated region (UTR) of NUMB precursor-mRNA (pre-mRNA) and also competing with eukaryotic translation initiation factor 4 γ1 (eIF4G1) for binding to poly(A) binding protein cytoplasmic 1 (PABPC1)
a | O-GlcNAc transferase (OGT) may achieve some level of substrate specificity through its amino-terminal tetratricopeptide repeat (TPR) domain
Microglial derived signals determine NSC survival and differentiation in EAE
Both endogenous and synthetic cannabinoids elicit their effects by binding to CB1Rs (, , , )
Both endogenous and synthetic cannabinoids bind to CB2Rs
A. Stimulation of AC and PKA potentiates the N-acyltransferase (Ca2+-dependent transacylase, CDTA).
Low-dose IL-2 selectively activates high-affinity IL2R-expressing Tregs, but has limited effect on Teffs
Cartilage damaged by trauma, mechanical stress such as obesity, and chronic inflammation initiates the release of DAMPs including HMGB-1, AGEs, and S100A8 and S100A9 calgranulin proteins
Proposed model of pleiotropic roles of Ca+2/calmodulin-dependent (CAMK) pathways regulating cadmium toxicity in human osteoblast-like cells
Activation of Gq/11 protein-coupled receptors (GqPCR) mobilizes 2-AG through the activation of phospholipase C (PLC), generation of diacylglyercol (DAG), and conversion of DAG to 2-AG by DAG lipase (DAGL)
Diagrammatic representation of hypothesized molecular mechanism of LH signaling dysfunction in PCOS women modified from []
General signaling cascades responsible for downstream activation of TLRs
Network of selected factors influencing myofibroblast survival/resistance to apoptosis
The protective role of autophagy pathway in AD pathogenesis
The protective role of the FOXO pathway in aging and AD pathogenesis
The role of the IR/Akt/mTOR signaling pathway in promoting aging and AD pathogenesis
The protective role of the SIRT pathway in aging and AD pathogenesis
The controversial role of the hypoxia/HIF signaling pathway in aging and AD pathogenesis
The role of the ROS pathway in aging and AD pathogenesis
The protective role of the AMPK pathway in aging and AD pathogenesis
Genes mutated with > 2.5pct mutation frequency in the Axon guidance pathway (KEGG).
Schematics representing different tissues using varied forms of cellular communication within a lineage hierarchy (solid arrows indicate cell lineages; dotted arrows represent signaling between different cells)
Ethanol upregulates TNF-Œ± in Kupffle cells via the activation of multiple pathways Ethanol administration activates the TLR4 pathway, ROS production and complement activation to increase the expression of TNF-Œ±
(A) APOL1 enters the trypanosome as a component... (B) Studies overexpressing APOL1 in human cells... (C) Other investigators found that overexpresse...
Upon binding to CD47, TSP1 activates the Nox1 complex, which generates robust and sustained accumulation of ROS
Schwann cell laminins influence multiple cellular events that are necessary for normal Schwann cell development, including survival, proliferation, radial sorting, and myelin wrapping
Central nervous system (CNS) laminins influence multiple steps during oligodendroglial development, including differentiation and myelin wrapping
NO, in the presence of oxygen postranslationally modifies proteins via S-nitrosation
In mammals, IGF-1 is produced primarily in the liver in response to growth hormone secreted by the pituitary gland
Cell cycle progression: JARID1A and JARID1B promote G1-S progression through repression of CDK inhibitors and Cyclin D upregulation
This illustration summarizes some of the mechanisms by which a stiff ECM or augmented cellular tension may alter tumor cell fate
In the atherosclerotic lesion, in areas where nutrients are sufficient, increased inflammatory mediators and modified LDL cause reduced LKB1 levels through LKB1 degradation in macrophages
A) Heatmap schematic illustrating fold change in expression of all genes associated with NF-κB signaling that were identified as being significantly up- or down-regulated in the brain following TBI in Nlrx1−/− mice compared to the TBI wild type animals
NMD degrades mRNAs encoding UPR components
NMD and apoptosis have a complex regulatory relationship I
A diagram showing LMP1 signaling transduction to IRF4 activation
A functional riboflavin synthesis pathway is found in commensal and pathogenic species, which can lead to MR1-dependent presentation of metabolites to MAIT cells
(A) NFKB signaling pathway analysis using Ingenuity Pathway Analisis (IP... (B) Network of genes known to interact with phosphatidylserine and phosp...
Summary of pathways and signals discussed in this review that induce NK cell activation and/or NKG2D ligand expression in tumor cells and in virus-infected cells
SCO1 function is integral to a mitochondrial signaling pathway that impinges upon copper homeostasis
Glycerolipid biosynthetic pathway enzyme localization to subcellular compartments
The canonical pathway by which an extracellular growth factor (GF) binds a receptor tyrosine kinase (RTK) to activate transcription in the nucleus is depicted
A. Oncogenic RAS induces expression of both RPL23 and p19ARF independently.
Rationale for mTOR inhibitor + NOTCH inhibitor combination
In single-celled beings, nutrients are utilized when available for proliferative metabolism and when nutrients are limiting cells undertake a fundamentally different, starvation metabolism
Intercellular and intracellular signaling pathways converging on HSF1At the organismal level, HSF1 is subject to cell non-autonomous regulation by neuronal signaling (serotonin), insulin/IGF-1 signaling, germline stem cell (GSC) signaling and transcellular chaperone signaling
Extracellular LPS is recognized by TLR4/MD2 complex, and triggers MyD88- and TRIF-dependent signaling cascades
(A) LEGSKO lens epithelia. (B) BSO-treated LEGSKO lens epithe... (C) LEGSKO lens fiber cells. (D) BSO-treated LEGSKO lens fiber...
Working model of the mechanical response pathway by which pressure and shear stimulate tumor cell adhesion
Clearance of AICAR through the de novo purine synthesis pathway limits effectiveness of AICAR as an AMPK activator in skeletal muscle
mTORC1 is a large multiprotein complex containing mTOR and Raptor, which phosphorylates and activates S6 kinase-1, an activator of protein synthesis, and phosphorylates and inactivates initiation factor 4E-binding protein-1 (4E-BP1), an inhibitor of protein synthesis
(A) Individual G protein- and βarrestin-mediate... (B) Conceptual model for GHSR1a regulation of V... (C) Model of the effect of a genetic ablation o...
IL-15 is transpresented in association of IL-15 RŒ± to the IL-2 receptor β and γc subunits, leading to phosphorylation and activation of Janus kinase 1 (Jak1) and Jak3, respectively
Scopolamine or VU0255035 blockade of ACh-M1 receptors located on GABAergic interneurons results in disinhibition and a burst of glutamate that activates AMPA receptors
Hepcidin expression is regulated by iron signals (middle), erythropoiesis (left), and inflammation (right).High iron stores augment BMP6 (bone morphogenetic protein 6), which together with its co-receptor hemojuvelin (HJV) activates type 1 (Alk2/3) and type 2 (BMPR2, ACVR2A) BMP serine threonine kinase receptors, leading to phosphorylation of receptor-activated SMAD (R-SMAD) proteins and formation of active transcriptional complexes with SMAD4.
Summation of the proteomic values for the ERBB2− sample set for genes present in the regulation of actin cytoskeleton pathway for ERBB2− set from KEGG
(a) An aberrantly reactivated complement-microg... (b) C1q promotes aging-related inflammation and... (c) Factor H promotes subretinal inflammation i...
Pathway alterations in glioblastoma multiforme
NADP+ is generated by the glutathione redox pathway in which GSH peroxidase (GPx) reduces H2O2 and oxidizes GSH to GSSG, which is reduced back to GSH by glutathione reductase (GRed) accompanied by the generation of NADP+
A) Amplification of EGFR activates mTORC2, AKT, and c-Myc to promote met... B) AKT and c-Myc (in green) activate enzymes (in blue) involved in glyco...
Glucose enters the β cell via GLUT transporters and is converted to glucose-6-phosphate (G6P) by glucokinase (GK), the first, committed step of glycolysis
Lipid metabolites, including fatty acids (FA), activate cell surface G protein-coupled receptors (GPCR) such as Gpr40, Gpr120 and Gpr119, or enter the β cell via transporters (CD36)
Model illustrating the intracellular signaling pathway leading to cell proliferation and survival in response to NRG-1β treatment
Cartoon depiction of a neuronal post-synapse
Working hypothesis of succinate-mediated GPR91 activation pathway in the retinal ganglion cells during the development of DR, ROP, and hypoxic retinal diseases ( adopted from doctoral dissertation of Jianyan Hu, School of Medicine, Shanghai Jiaotong University )
(A) Schematic overview of the major synthesis and degradation pathways for PtdIns-3-P (PI3P), PtdIns-3,4-P2 and PtdIns-3,4,5-P3
The processes inhibited by different classes of mTOR inhibitor are shown
In lymphocytes, FOXO transcription factors have prominent roles in differentiation
Adaptive resistance (in green, also labeled “1”) often involves upregulation of upstream regulators, including RTKs (HER3, INSR, IGF-1R), IRS-1, JAK2, or SRC by disruption of negative-feedback loops
Schematic representation of PIK3CA cellular signaling pathway
Schematic representation of major steps of SILAC analysis to identify phosphopeptides that are altered after treatment with MELK inhibitor OTSSP167 in melanoma cell lines (A375 and M14)
Activated MAP kinase signaling pathway leads to the upregulation of MELK expression via the transcription factor E2F1
The role of cyclin–CDK complexes and the cyclin D–CDK4/6–p16–Rb pathway in the cell cycleThe cell cycle is regulated by cyclins and checkpoints, with different cyclins (and cyclin–CDK combinations) and checkpoints acting at phase transition of the cell cycle
Interferon signaling in HPV-containing keratinocytes
a) BCL-2 family proteins regulate the intrinsic pathway of apoptosis and... b) Antiapoptotic proteins are often overexpressed in cancer cells, where...
A, NTS‚ÜíPVN GLP-1 signaling affects food intake
Integration of signaling changes after the induction of BP1
(a) Phosphorylation (represented by −P) of Rps6 has been observed downstream of multiple growth signals and pharmacological stimuli
The membrane-bound EGFR can activate three major branches of protein kinase pathway, leading to profound changes in both the cytoplasm and the nucleus to influence cellular phenotype at tissue and organismal levels
(a) Hyperactivated EGFR signaling activities co... (b) Amplified and hyperactivated EGFR can also... (c) In the brain, hyperactivated EGFR increases...
Quiescent cells express PDGFRŒ± in primary cilia
In the canonical pathway, when the Frizzled receptor is not activated, the destruction complex (Apc and Axin) binds β-catenin inducing its phosphorylation as mediated by GSK-3β and CKI, which results in β-catenin degradation
IL-17A/IL-17F/IL-17A/F binding to the receptor complex enables homotypic interactions between the SEFIR domains in the receptor and in the adapter Act1/CIKS
Microglia, the primary immune and cytokine-producing cells of the central nervous system (CNS), are also critical for normal brain development via (A) the phagocytosis of extraneous synapses using the complement pathway; (B) releasing factors such as BDNF and IL1β critical for synapse formation during learning and memory; (C) phagocytosis of neural progenitor cells (NPCs) via the TREM2 and DAP12/CD11b pathway; (D) assisting in neuronal differentiation via the release of insulin-like growth factor-1 (IGF-1); (E) Neuronal patterning and wiring using Cx3cr1 signaling; (F) supporting neuronal growth and survival by releasing trophic factors; and (G) inducing programmed cell death via nerve growth factor (NGF), CD11b integrin DAP12 immunoreceptor
The recognition of fungal molecules, such as β-glucans, α-mannans, and glycoplipids, by C-type lectin receptors (Dectin-1, Dectin-2, Dectin-3, and MINCLE) induces the assembly of a CARD9-BCL10-MALT1 complex, which mediates the activation of NF-κB and MAPK signaling, leading to the translocation of NF-κB and AP-1 into the nucleus
Formation of autophagasomes in autophagy
Several mechanisms have been shown to regulate TEAD transcriptional activity
Three main classes of regulatory small RNAs
The NF1 protein, neurofibromin, functions as a GTPase-activating protein (GAP) for p21-RAS, accelerating its conversion from an active RAS-GTP bound molecule to an inactive RAS-GDP bound form
Simplified schematic depicting the mTOR pathway and associated “mTORopathies.” The mTOR pathway involves 2 complexes, mTORC1 and mTORC2
Typically, the Kdo2-lipid A domain of LPS or LOS is required for growth of gram-negative bacteria
The mitochondria-mediated intrinsic pathway is activated in response to stress stimuli
HBV DNA polymerase (Pol) binds to DDX3 to suppress the activation of IRF3 and, although HBV pgRNA activates RIG-I to induce type III IFN via MAVS, TBK1 and IRF3, the binding of HBx to MAVS disrupts the RIG-I signaling pathway
Central carbon metabolism and one-carbon metabolism play critical roles in melanoma biology
Plasma membrane damage activates the CWI pathway and the Ca2+-dependent signaling cascade in budding yeast.Purple circles indicate the components of the CWI pathway
A working model of the plasma membrane damage checkpoint.The plasma membrane damage checkpoint activates the CWI pathway and the Ca2+-dependent signaling cascade
Homeostatic mechanisms guiding cellular adaptations are directed by the hypoxia inducible factor (HIF) signaling pathway
A schematic presentation of different pathways involved in PCa disparity.1
Epithelial PGR regulates multiple signaling pathways in the endometrium and transuduce signals via uterine epithelial-stormal inteactions
TLRs differentially recruit specific sets of TIR domain-containing adaptor molecules like MyD88, TRIF, TIRAP/MAL, or TRAM
Oxidative stress leads to the generation of lipid peroxidation products, ROS, free radicals in lung cell types
Genomic mechanisms, including gene transactivation (A) and transrepression (B), are the best characterized means of LXR activity in cells, whereas recently described non-genomic mechanisms (C) remain somewhat less well understood
The in vivo pathways for disposal of excess cellular – in this case, macrophage – cholesterol from the organism, so called ‘reverse cholesterol transport,’ are depicted
E2 rapidly initiates signaling through membrane associated ERα that complexes with and signals through metabotropic glutamate receptor 1a (mGluR1a)
Platelet-derived growth factor-BB (PDGF-BB) secreted by endothelial cells binds to the PDGF receptor-β (PDGFRβ) on pericytes, causing receptor dimerization, autophosphorylation, and activation
Pericytes (left, pink) – Tumor growth factor-β (TGF-β) secreted by endothelial cells and pericytes binds to TGF-β receptor 2 (TGFβR2) that phosphorylates activin-like kinase 5 (Alk5) (inhibited by Smad7) activating the downstream Smad signaling cascade
Astrocytes (top left, green) secrete apolipoprotein E (APOE) 2 and 3 that bind to pericyte lipoprotein LRP1 receptor (bottom, orange) to inhibit downstream CypA-NFŒ∫B-MMP-9 pathway
The Wnt pathway can be classified as canonical and non-canonical
Canonical Wnt Pathway and Inhibitors of the Wnt/beta-Catenin Signaling Pathway schematic representation of the Canonical Wnt Pathway and pharmacologic inhibitors of the Wnt/beta-catenin signaling pathway
Non-Canonical Wnt Pathway and the Notch and Sonic Hedgehog Pathway-The two major non-canonical pathways are Wnt/calcium and Planar Cell Polarity (PCP) pathways
Cross-Talk between the Wnt, Notch and Sonic Hedgehog Pathways- Beta-catenin can drive activation of Notch signaling by increasing expression of the JAG1 gene, which encodes the Notch ligand Jagged1
Depicted regulatory interactions (arrows) at the indicated stages of life are based on germ line or conditional loss of function data for each indicated TF
(A) Schematic representation of the canonical PI3-kinase signaling pathway
Several mechanisms have been proposed for CSPG-mediated neurite growth inhibition
Apoptosis signaling pathway with green indicating genes with no change in expression between antral follicle stages, white indicating genes with no detectable expression or absent from the microarray chip, orange indicating genes with an increase in expression and blue indicating genes with a decrease in expression
Transforming growth factor-beta (TGFβ) signaling pathway with green indicating genes with no change in expression between antral follicle stages, white indicating genes with no detectable expression or absent from the microarray chip, orange indicating genes with an increase in expression and blue indicating genes with a decrease in expression
Transcripts corresponding to most genes present in the KEGG Cell Cycle Pathway were increased in abundance in CCDs from rats on Day 2 of development of vasopressin-escape
Schematic drawing showing the effects of IGF-1 and ALC on prepubertal Kp synthesis and release
Schematic depicting β2AR-mediated ERK activation
MEP increases phospho-activation of Src and Pyk2 by day 2 of treatment
TumorMap framework and application to the analysis of the TCGA Pan-Cancer-12 Dataset
Activation of NF-Œ∫B (nuclear factor-Œ∫B) by canonical and atypical pathways
a | Under unstimulated conditions, newly synthesized NF-κB-inducing kinase (NIK) is rapidly bound by TNFR associated factor 3 (TRAF3) and targeted for ubiquitylation (Ub) by the cellular inhibitor of apoptosis (cIAP)–TRAF2–TRAF3 E3 ubiquitin ligase complex
Immune responses to protein antigens involve the formation of germinal centres (GCs) within B cell follicles, in which activated B cells undergo clonal expansion and a series of differentiation events, which leads to the generation of antibody-secreting plasma cells or memory B cells
Naive T cell activation via the T cell receptor (TCR) and signalling through the co-receptor CD28 leads to the rapid activation of the canonical nuclear factor-Œ∫B (NF-Œ∫B) pathway, which contributes to the initial activation and clonal expansion of T cells
Under physiological conditions, non-canonical nuclear factor-Œ∫B (NF-Œ∫B) signalling mediates the survival and homeostasis of B cells, the generation and effector function of T helper 17 (TH17) cells, the differentiation of osteoclasts from monocytes, chemokine production in endothelial cells, and glucagon responses in hepatocytes,,,,,,,
PI3K-AKT-mTOR signaling pathways in glioblastoma
Hepatocyte growth factor (HGF) activation of the MET receptor tyrosine kinase releases β-catenin (CTNNB1) from surface cadherin molecules
Neurons. Nitric oxide (NO) is a major moderator of functional hyperemia.
Neuronal ATP can activate P2XRs on astrocytes to produce AA via phospholipase D 2 (PLD2)-mediated production of diacylglycerol (DAG) and subsequent metabolism by DAG lipase (DAGL)
The intracellular bacteria Brucella abortus enters the host cell and ensures its survival by forming the Brucella-containing vacuole (BCV)
(Left) KRAS enhances ATF4 mRNA levels through PI3K-AKT mediated NRF2 up-regulation
A potential cascade of molecular events leading to reduced differentiation of regulatory T cells for prevention of autoimmunity
a | B-cell receptor (BCR) signalling activates the inhibitor of nuclear factor-Œ∫B (NF-Œ∫B) kinase (IKK)‚ÄìNF-Œ∫B signalling pathway through the CARMA1‚ÄìBCL-10‚ÄìMALT1 signalosome
In many types of leukemia, STAT5 and/or STAT3 are constitutively activated by JAK2 signaling from receptors of diverse cytokines/growth factors, or directly by JAK2V617F, a hallmark of myeloproliferative neoplasms (MPN)
In primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (HL) (top panel), autocrine IL-13 signaling and chromosome 9p24 amplification result in JAK2 constitutive activation
Pathway affected commonly in liver metastases irrespective of cancer types
The effects of different inhibitors ( and ) indicate that nociceptin effects on GLAST expression are mediated by a signaling cascade that involves the interaction of PI-3K/AKT, mTOR and JAK
a) Dendritic epidermal T cells (DETC) are capable of responding to bacte... b) The microbiome conditions γδ IEL effector functions through an intest...
Cancer cell metabolic changes linked to hyper-O-GlcNAcylation
Schematic illustration of a simplified version of the EGFR signaling pathway, in which only the key molecules included in the model are displayed
Frizzled (Fzd) Wnt receptors form ligand-dependent heterodimers with the LDL receptor related proteins LRP5 and LRP6 to convey canonical signals conveyed by nuclear β-catenin
Activation of NMDA receptors (NMDARs) and L-type voltage-sensitive calcium channel (Cav1.2) triggers calcium influx and induces calcium-dependent signaling molecules such as calcineurin (CaN) and Ca2+/calmodulin-dependent protein kinases (CaMKs).
Model for TRAIL induced apoptotic pathway with involvement of cathepsin B
RNA from peripheral blood of AD patients (n=9) and healthy controls (n=10) were assayed by genome-wide gene expression microarrays
a| Under fasted conditions, glycogenolysis is activated and glycogen synthesis is suppressed
Inactive AhR is localized in the cytosol complexed to HSP90, AIP, p23 and c-SRC
In HEK293T cells with wide-type RKIP expression, RKIP bound to ANXA7 and blocked SEC-induced ANXA7 GTPase activation
Ingenuity Pathway Analysis of mitochondrial proteomic networks influenced in the IFM by nano-TiO2 exposure (A) and preserved in the IFM of mPHGPx nano-TiO2 exposed (B)
(A) Indirect regulation of BCR signaling through cAMP
Activation of VEGF receptor 2 (VEGFR2) induces cell proliferation, migration and survival, and vascular permeability, leading to angiogenesis
Activation of synaptic NMDAR mediates survival pathway and induces LTP and LTD
Schematic diagram of proposed sst2signaling pathway involved in SST-induced hyperpolarization of subicular BCs
Binding of RANKL to the RANK receptor on the cell surface of osteoclasts initiates a complex signaling pathway which involves TRAF6, TRAF3 and c-Fos proteins
Ingenuity Pathway network showing significant pathways (P-value ‚â§0.05) enriched by VvInt correlated transcripts
(a) (Left) DBF4-dependent kinase (DDK) and cycl... (b) When a replication fork is stalled, nearby... (c) It is unclear how ATR allows dormant origin...
Signaling via the IL-7 receptor (IL-7R) maintains Glut1 expression, glucose uptake, and mitochondrial OXPHOS in naïve CD4+ T cells
CD81-positive EVs secreted by cancer-associated fibroblasts (CAFs) enhance motility, protrusion and invasion in breast cancer cells via the autocrine Wnt-PCP signaling pathway
(A) Various differentiation programs are initiated by the ubiquitylation and degradation of transcriptions factors that are targeted by the indicated CUL3-based ubiquitin ligases
Vigabatrin (VGB) accumulates and increases GABA in the eye, resulting in molecular/cellular alterations in the mTOR pathway and GABAergic/glutamatergic receptor expression
The dermal cone/fat dome structure and its role in burn-related HTS pathogenesis
Growth factor/PI3K/AKT signaling stimulates glucose uptake and flux through the early part of glycolysis
In the presence of ANKRD11, Histone H3 and p53 are acetylated in the promoter regions of dendrite-associated genes such as Trkb, which results in transcription of the genes
The critical difference between the active (A) and inactive (B) states of the canonical WNT signaling pathway is the accumulation of the licensing factor β-catenin, especially in the nucleus, where it binds to TCF/LEF family transcription factors to promote changes in gene transcription
A network of the top three canonical pathways (Phospholipase C Signaling, Role of NFAT in Regulation of the Immune Response, GŒ±q Signaling) and its associated differentially expressed genes was generated
The complement cascade is initiated via pattern recognition proteins (PRPs) of the classical pathway (CP) and lectin pathway (LP) or via tick-over of the alternative pathway (AP)
Downstream mTOR effectors in PVR categorized by disease stage (left)
TUSC2 has been show to regulate diverse cellular processes, including cell cycle arrest, apoptosis, calcium homoeostasis, oxidative stress response, immune response, miRNA expression, transcriptional regulation, p53/MDM pathway, and tyrosine and Ser/Thr kinases
Relationships between metabolome, proteome, and genome in metabolic reprogramming of endothelial cells in PH
With an appropriate signal, Prdx6 is phosphorylated via mitogen activated protein kinase (MAPK) activity and binds to phospholipid in the cell membrane
Two B-hyperpaths computed in the full NCI-PID signaling pathway
Small Wnt Pathway Solutions to nuclear β-catenin, denoted by a compartment marked ‘n’ for nucleus
BAs are produced from cholesterol, enter bile canaliculi via BSEP and MRP2, empty into the duodenum upon stimulation of the gallbladder with CCK, get mostly reabsorbed in the terminal ileum via ASBT, then shuttled into the portal vein via OSTŒ±/β where they are recycled back to the hepatocyte
PSY is a byproduct of metabolism of galactosylceramide (GalCer), one of major glycosphingolipids of myelin
Major mechanisms of therapeutic resistance to androgen axis-targeting therapies in prostate cancer
High and low GnRH pulse frequencies stimulate different signaling pathways to mediate the synthesis of transcription factors and repressors controlling Lhb transcription
High and low GnRH pulse frequencies stimulate different signaling pathways that mediate the synthesis of transcription factors and repressors controlling Fshb transcription
Recent mechanistic insights into the pathophysiology of antiphospholipid antibodies (aPL) and APS
(a) Western blot analysis of Sp1 expression in... (b) Western blot analysis of B16F1-Met cells tr... (c) Mechanical pathway of Ezrin transactivation...
Novel therapies for age-related diseases target key cellular processes in ageing cells
The two-signal model of T-cell activation
Nrf2 plays a pivotal role in protecting osteoarthritis chondrocytes against IL-1β-induced oxidative stress and apoptotic events through inhibition of extrinsic apoptosis (caspase-8) and intrinsic apoptotic pathways (caspase-9 and 3), mitochondria dysfunction, release of cytochrome-c in cytosol, expression of pro-apoptotic proteins-Bax and Bad and stimulation of anti-apoptotic proteins-Bcl-2, Bcl-xl and Mcl-1 via activation of ERK1/2/ELK1-P70S6K-P90RSK signaling axis in human OA chondrocytes
Schematic illustration of the basic humoral and cellular elements that evoke tumour cytolysis in the context of monoclonal antibody (mAb)-based cancer immunotherapy
Ceramide is the central molecule in sphingolipid metabolism and can be synthesized de novo (dark blue boxes) by the functions of serine palmitoyl-transferase (SPT), 3-ketosphinganine reductase, (dihydro)ceramide synthases (CERS1–6) and dihydroceramide desaturase (DES)
(A) Schematic pathway diagram of carbohydrate metabolism, and list of 51... (B) Schematic overview of the combinatorial CRISPR-Cas9 screening approa...
A) Mutations in PHEO/PGL susceptib... B) Kinase signaling cluster includ... C) Recently, the Wnt signaling pat... D) Mutations in SDHx and FH genes...
FA signaling is composed of all signaling transductions involving one or more FA proteins
Upon translation and entry into the secretory pathway, Wnt proteins are acylated by Porcn and ushered out of the cell via Wls
Metabolism-mediated modification of pro-apoptotic proteins
DJ-1 activates the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway to mediate cell survival, proliferation, and autophagy
1. 6-Hydroxydopamine-induced oxidative stress may upregulate DJ-1 through activation of ERK1/2 ()2.
1. DJ-1 increases phosphorylated Akt, and activates the PI3k/Akt pathway, which contributes to oncogenesis and neuronal survival (; ; ; )2.
Main intracellular pathways involving key signalling molecules activated upon binding of granulocyte-colony stimulating factor (G-CSF) to G-CSF receptor (G-CSFR)
Neurotransmitters, growth factors, cytokines and hormones (insulin) activate their membrane-bound receptors to recruit the phosphatidylinositol-3-kinase (PI3K)/Akt and Ras/extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathways and activate mTORC1 and mTORC2
The canonical NF-Œ∫B pathway is regulated both by K63 (Lys63)-linked and linear (Met1)-linked ubiquitin chains
The mTOR signaling pathway and the cell cycle pathway associated with lung adenocarcinoma as reported in
Notch1 can be activated in IR-stressed livers
Role of Ang II signaling in adverse myocardial remodeling
Schematic of the Toll-like receptor (TLR) signaling pathways in the prefrontal cortex
A. Increased activity of the PI3K/AKT/mTOR pathway.
Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway that results in the synthesis of cholesterol and isoprenoids
A. Following Wnt ligand binds to co-receptors LRP5/6 and Frizzled, the Wnt/β-catenin pathway is activated and β-catenin is freed from the APC/Axin destruction complex and translocates into the nucleus where it activates Wnt-target gene transcription.
Mode of BMP signaling determines Smad dependent and independent pathways
Following rapid activation of TLRs, NF-Œ∫B induces miR-210 expression in microglia/macrophages; however, miR-210 serves as a negative feedback regulator for the M1 activation by targeting NF-Œ∫B
a). Scheme 1- Similarities between type 2 diabetes and type 3 diabetes (... b). Scheme 2 - Understanding of interaction of enzyme (BuChE), substrate...
This diagram is consistent with only one turn through the TCA cycle
Proposed mechanism by which PKCŒ± regulates Ca2+ sparklet activity in arterial myocytes
Following infection, multiple host sensors have been shown to respond to alphavirus infection
The IGF-1R is activated by its ligand IGF-1 and by mechanical loading
Pathways leading to IL-24 induction shown with red arrows
Extracellular signaling pathways, generated in human and mouse embryonic stem cells (hPSCs and mPSCs, respectively), muscle satellite stem cells (MuSCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and neural stem cells (NSCs) modulate intracellular metabolic pathways
(A) Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are natural compounds that effectively enhance NAD+ biosynthesis and have health benefits
The nocturnal increases in melatonin levels during the night activated MT1signaling which affect the transcription of the genes that are responsible for the assembly and the activity of P13K and thus glucose uptake
Statins as a class inhibit endogenous cholesterol production by competitive inhibition of HMG-CoA reductase (HMGCR), which catalyzes conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol synthesis
Mechanism of PD-1 and PDL-1 pathway in tumor environment and the complex crosstalk between cancer, tumor, T-cell, APC and macrophage and tumor stroma
Regulation of canonical and noncanonical pathways of NF-Œ∫B activation by cylindromatosis (CYLD)
Classical pathway of complement activation initiates with antibody binding and recognition by the C1q/r/s complex to cleave C2 and C4 to form a C3 convertase (C2aC4b; blue box)
Putative model illustrating the interplay between RANK/NFŒ∫B-dependent and Hdac3-dependent control of mTEC development
Visualization of changes in gene expression after 1,25(OH)2D treatment in THP-1 cells, DCs and monocytes
WikiPathways representation of A) cell cycle; B) DNA replication pathways
Endurance exercise leads to the activation of AMPK and consequently to increased coactivation of PPARβ/Œ¥ by PGC-1Œ±, resulting in improved mitochondrial oxidative function
The three major players that regulate FSH subunit gene transcription include GnRH, activin-inhibin-follistatin and steroids
A: Non-Canonical Wnt-signaling: Non-canonical Wnt/PCP (planar cell polarity) pathway
This figure summarizes the different Wnt pathway modulators with variable specificities and at different stages of development (fully described in the main text)
(A) Schematic of death receptor-mediated apoptosis in response to TNF. T... (B) Schematic of death receptor-mediated apoptosis in response to FasL/T...
A decrease in perfusion pressure activates the renal baroreceptor, stimulating renin synthesis and release
Cell specific APC protective signaling pathways
Proposed potential therapeutic targets in Erythroleukemia
A schematic of the predicted signalling pathways for HagB-induced MMP production in dendritic cells
How radiation impacts tumor and immune cells to modulate the immunological response
Part I) the FA proteins (FANCA, B, C, E, F, G, L,... II) FANCD2 and its paralog FANCI, as a centra... III) downstream of Part-II, the remaining FA...
In intestinal epithelial cells, rotaviruses are recognized by the pattern recognition receptors (PRRs) probable ATP-dependent RNA helicase DDX58 (RIG-I) and interferon (IFN)-induced helicase C domain-containing protein 1 (MDA5)
a | In the classic IL-6 signalling pathway, IL-6 binds to the membrane-bound IL-6 receptor-α (subsequently referred to as IL-6R), thus inducing formation of a heterohexameric complex consisting of two molecules each of IL-6, IL-6R, and the IL-6 receptor subunit-β (gp130)
JAK proteins bind to the Box 1 and Box 2 domains in the intracellular portion of IL-6 receptor subunit-β (gp130)
TLR4-MyD88 signaling results in NF-Œ∫B activation and production of pro-inflammatory cytokines such as TNFŒ± and IL-6
Metabolism plays an important role in T cell proliferation and differentiation and dysregulation of metabolism is often linked to autoimmune diseases
The urea cycle allows cellular disposal of nitrogen from mitochondrially catabolized glutamate via mitochondrial conversion to carbamoyl phosphate, citrulline shuttling to the cytosol, and loss of urea from arginine
Androgen synthesis is catalyzed by the enzyme CYP17
Regions (outlined in grey): third ventricle (3rd V), arcuate nucleus of the hypothalamus (ARH), ventromedial hypothalamus (VMH), lateral hypothalamus (LHA), paraventricular nucleus of the hypothalamus (PVN), nucleus of the solitary tract (NTS), ventral tegmental area (VTA), nucleus accumbens (NAc), dorsal striatum (DS)
Phosphatidylcholine (PC) metabolism and Alzheimer’s disease (AD)
The mTOR signaling pathway with potential contributions from GABA and Glu receptors
Hydrogen sulfide (H2S) and nitric oxide (NO) are generated by enzymatic and non-enzymatic pathways
Vasoconstrictor agonists through Gq/11/phospholipase Cβ (PLCβ) increases [Ca2+]i and causes contraction through calcium-calmodulin (CaM)/myosin light-chain kinase (MLCK) pathway (1)
In human HCT116 and SW480 CRC cells (left), agonism of FFA4 modulates proliferation and cell migration
Mesenchymal stem cells (MSC) localized to the tumor microenvironment produce 16:4(n-3) PUFA in response to platinum-based chemotherapeutics such as cisplatin via an intracellular signaling mechanism that is dependent on Ca+2, PLA2, thromboxane synthase (TXAS), and cyclooxygenase-1 (COX1) ()
Possible cellular mechanisms involved in calycopterin-induced apoptosis in HepG2 cells
mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) are two functionally and structurally distinct complexes
Folate enters the cell through receptor-mediated (folate receptor alpha [FRŒ±], gene FOLR1; beta [FRβ], gene FOLR2; or gamma [FRγ]) or carrier-mediated (solute carrier family 19, member 1 [SLC19A1]) transport mechanisms
Inhibition of the BRCA1 DNA damage response pathway indicated by a down modulation (green; up-modulation is indicated in red) of atm, brip1, cdkn1a, e2f3, fancd2, fancl, mdc1, rad51, and rpa1 in male X
KSHV activates the PI3K and ERK1/2 pathways during infection, which are heavily reliant on kinases (drawn as circles) to propagate the signaling cascade
Irisin stimulates the browning of white adipose tissue (WAT) by inducing the expression of UCP1 gene and, consequently, of UCP1 protein via the p38 mitogen-activated protein kinase (MAPK) and extracellular-signal regulated kinase (ERK) pathway
Irisin can activate the AMP-activated protein kinase (AMPK) pathway by reducing intracellular ATP levels, or by increasing reactive oxygen species (ROS) or intracellular calcium concentrations
Irisin reduces gluconeogenesis by downregulating the expression of PCK1 (also known as PEPCKC) and G6PC via AMP-activated protein kinase (AMPK) and the phosphoinositide 3-kinase (PI3K)–AKT–FOXO1 signalling pathway
In the classic nuclear signaling pathway (1) progesterone activates progesterone receptor (PR) by binding and inducing conformational changes of the receptor causing in turn nuclear translocation, dimerization and binding to progesterone response elements (PRE) in the promoters or enhancer regions of PR target genes
Pathogenic microorganisms are sensed via Toll-like receptors (TLR) and NOD-like receptors (NLR) on innate immune cells (dendritic cells (DCs), macrophages), Paneth cells and epithelial cells
AMP binding activates AMPK by three effects, i.e.
(A) The binding of CXCL12 to its cognate receptor, CXCR4 initiates the a... (B) Agonist-induced heterodimerization of CXCR4 and CB2 inhibits GŒ±13 a...
From left to right: (A) Prosurvival action of AKT signaling: AKT phosphorylates and inhibits pro-apoptotic proteins in the cytosol and phosphorylates and causes dislocation of the FOX3O transcription factor from the nucleus; (B) Signaling by growth factor receptors leads to the activation of the prosurvival MAPK ERK1/2 pathway and to the induction of prosurvival transcription factors; (C) Stress factors lead to the activation of the stress-induced MAPK pathways JNK1/2/3 and p38, which leads to the induction of pro-apoptotic c-Jun activation and phosphorylation of tau protein; and (D) Activation of the JAK-STAT pathway by cytokines leads to the dimerization of cytokine receptors, phosphorylation of the associated with them JAK kinases, subsequent phosphorylation of STAT transcription factors and dissociation of the phosphorylated STAT transcription factors in the cell nucleus
During cellular oxidative stress, especially vascular oxidative stress, a host of cellular pathways are activated that directly result in the enzymatic formation of ROS and reactive nitrogen species (RNS), ()
A cartoon schematic showing the mTOR signaling pathway in cells
Postprandial delivery of choline, phosphatidylcholine (PC), carnitine, γ-butyrobetaine, and likely other methylamine-containing source nutrient gut microbes provides substrate for the gut-microbial-mediated production of trimethylamine (TMA)
In the latent state, the 5‚Ä≤LTR NF-Œ∫B and NFAT binding sites are occupied by inactive p50 homodimers, while the active p50/p65 NF-Œ∫B isoform is bound to IŒ∫B and sequestered in the cytoplasm
Both medaka (A) and zebrafish (B) up-modulate the complement signaling pathway (IPA z-score 2.4 in medaka and 2.0 in zebrafish) in skin following FL exposure; however, only zebrafish induce both the classical complement pathway (yellow box) and the alternate pathway whereas medaka only utilizes the alternate pathway.
Platyfish significantly down modulate the IGF signaling pathway leading to a suppression of cell proliferation, cell growth and cell survival in skin following FL exposure
The most significantly modulated pathway in medaka skin was the acute phase signaling pathway (IPA z-score 3.2) leading to an increase in the inflammation response; other pathways that play a role in the inflammation response such as IL-6 (boxed in yellow), ILK signaling (light blue), PPAR signaling (pink) and the Vitamin C pathway (dark blue) are also found within the acute phase signaling pathway
In zebrafish following FL exposure, the most significantly modulated pathway in skin is the oncostatin M pathway
Platyfish skin (A) significantly down modulates the PPARŒ±/RXRŒ± signaling pathway in response to FL; however, both medaka (B) and zebrafish (C) significantly up-modulate the PPARŒ±/RXRŒ± pathway in skin following FL exposure
Alterations in glucose and glutamine metabolism contribute to tumor growth and proliferation
The canonical PI3K/AKT/mTOR signaling pathway
PI3K and CDC42 pathways are not involved in ERK phosphorylation
Based on our data, we hypothesized that in the initial stage, UMSCC cell proliferation (both in the primary, UMSCC38 and secondary tumor, UMSCC11B cell lines) is achieved by TGFβ1/Smads/ŒîNp63/c-Myc pathway with higher proliferative attributes in UMSCC38
Sphingosine is produced from the sphingolipid pathway by the action of ceramidase on ceramide
Effect of Aβ on CypD-involved mPTP formation
Schematic representation of CTLA-4 and PD-1 molecular functions
Upon TCR and CD28 engagement, CTLA-4 is rapidly up-regulated and binds with high affinity to B7 molecules
Major efforts have been made in recent years to develop broad spectrum and/or organelle targeted antioxidant strategies, and enhanced autophagy, mitophagy, and lysosomal activities
(A) Genes mapped to the IL-6 pathway by IPA Software. Red, increased met... (B) List of genes mapped to the IL-6 pathway by IPA.
Phospholipases release arachidonic acid (AA) from the phospholipid membrane
A. Gravin forms signaling complexes with β2ARs and PKA.
A. LRRK2 regulation of striatal MSN spine morphology.
(Left panel) The blood-tumor-barrier associated with BCBMs has increased permeability mediated by desmin-positive pericytes and altered tight junctions
Owing to their lipophilic, detergent properties, bile acids can directly disrupt the plasma membrane and cause activation of PKC which in turn activates the p38 MAPK pathway
The M1 macrophage phenotype is pro-inflammatory and M2 phenotype is immunosuppressive
Anti-desmoglein autoantibodies can cause acantholysis through steric hindrance of desmoglein-mediated trans- (between molecules on opposing cells) and cis- (between molecules on the same cells) adhesion, inhibition of desmosome assembly and promotion of desmosome disassembly (by clustering and/or endocytosis of desmogleins) and stimulation of signalling pathways that can synergize with these mechanisms to modulate keratinocyte cell adhesion
MEK5/ERK5 pathway can be activated by stress, mitogens or cytokines, leading to the regulation of various downstream targets including kinases and transcription factors
Following its biosynthesis, PKC is in an open and degradation-sensitive conformation in which all its regulatory modules are unmasked (species i)
It is convenient to envision sphingolipid metabolism as organized into blocks
Purine salvage pathway and HGprt function ()
Therapeutic targets for brain injury for nanoparticle mediated drug delivery
Most literature’s figures available thus far illustrating molecular mechanisms underlying learning and memory depict only pre and postsynaptic neurons and relative mechanisms of interest
GCs stimulate GSK3ß and inhibit Wnt signaling
A. Targeting MUC1-C genetically or pharmacologically with the GO-203 inhibitor downregulates EZH2, SUZ12 and EED expression in TNBC, NSCLC and prostate cancer cells, demonstrating that MUC1-C induces multiple PRC2 components.
Using Reactome FI, a gene network was created using 322 genes with significant alterations in 5-hmC
Oscillation of NAD+ play an important role in modulating the functions of NAD+-dependent enzymes such as SIRT1, and poly(ADP-ribose) polymerase 1 (PARP1)
Interactions between cellular metabolism, the circadian molecular clock, and ion channels
A. Interstrand crosslinking (ICL) occurs.B.
A. In mouse embryonic fibroblasts (MEFs) and transformed cell lines, the genetic depletion of GCN5L1 reduced mitochondrial protein acetylation in parallel with induction of mitochondrial biogenesis (PGC-1Œ±) and lysosomal biogenesis (TFEB) regulatory programs.
Increased excitatory synaptic activity triggers Ca2+ influx through plasma membrane channels, resulting in the activation of multiple kinases, including calcium/calmodulin-dependent kinases (Ca2+/CaMK) and mitogen-activated protein kinases (MAPKs), nitric oxide synthase (NOS) and the protein phosphatase calcineurin
Intermittent metabolic switching (IMS) involves repeating time periods of a bioenergetic challenge (fasting and/or exercise) when the metabolic switch is on (that is, liver glycogen stores are depleted and ketones are produced) and recovery periods (eating, resting and sleeping) when the metabolic switch is off
Somatic drivers identified for COCA2 subtypes (top) cause the expression-level changes of key UBQ and DUB genes in SCF complex, APC/C complex, and DNA damage response that underlie the aberrant activities of cell-cycle and DNA damage pathways (middle), thereby leading to poor patient survival of COCA2 subtypes (bottom)
PA required for CL biosynthesis is imported from the ER to the OMM by an unknown mechanism
In the presence of Wnt ligands derived from the nail epithelium, osteoblasts that form the bone and precursors of osteoclasts that break down the bone both display Wnt pathway activation
Shh, Wnt and Fgf signaling promotes development of dbx1b-expressing dHb progenitors
Abnormalities in the tumour vasculature result in hypoxia and acidosis of the tumour microenvironment (TME), which in turn contribute to immunosuppression via several mechanisms
Using the MMTV-Myc mouse model, EMT and Papillary tumors were used in a proof of principle experiment to predict therapy
Cytosolic ROS are formed most notably through NOX activity and influence metabolic processes including glycolysis and downstream oxidative phosphorylation, pentose phosphate pathway activity and autophagy
PARP inhibition mechanism of action—blockade of the base excision pathway
MSC PGE2 secretion reprograms M1 via two independent pathways to M2 macrophages
In addition to the classical pathway involving glycolytic and oxidative metabolism of glucose to increase ATP:ADP ratio and inhibit KATP channels, our recent metabolomics studies identify two pathways that play complementary roles
In NF2/Merlin-mutant tumors, dysregulated CRL4DCAF1 and mTORC1 are two predominant oncogenic signaling nodes sustaining tumor growth
(A) Pathway diagram representing core metabolic... (B) Diagram of tumor-associated macrophage role... (C) Diagram of immune checkpoint pathway (featu...
Experimentally determined phosphorylated proteins at 5 min (green with orange P) with pathway proteins (blue) that were not experimentally observed to be phosphorylated after 5 min of mechanical strain
A: MRNA and protein levels of E-Cadherin (CDH1)... B: DW tRFs and mRNAs participating in MAPK sign... C: PPI network and DW associations of the corre...
(A) A balanced agonist binding to... (B) Biased agonism, or ‚Äòdruggabl... (C) Biased receptors, such as G pr... (D) System bias may be due to diff...
Type 1 diabetes pathogenesis and β cell protective factors
Finally, expression of T-cell co-stimulatory and co-inhibitory receptors can be modulated by hypoxia as well
(A) The list of regeneration genes from  and  with Z scores > 2.0 was as... (B) but for the “receptor binding” GO process.(D) Similar analysis as in
A) An episode of OGD-RP causes strong depolarization of CA3 PCs and neur... B) The proposed mechanism by which BDNF/TrkB counteract the deleterious...
Schematic outline of the involvement of necroptosis in elimination of cells of the cardiovascular system and reported inhibition strategies based on necroptosis pathway
Schematic representation of the Ras signaling pathway
MDSC differentiate from common myeloid progenitors (CMP), and follow the pathway that involves granulocyte-macrophage progenitor (not shown) and various intermediate progenitors and precursors including common monocyte progenitors (cMOP)
The figure depicts schematically the current consensus within the biology of aging community as to pathways that are important in order to target aging and indicates at which points metformin has been shown to have effects (see text)
Upon engagement with PD-L1 or PD-L2, PD-1 is phosphorylated at both thyrosine containing motifs ITIM and ITSM
During chronic infections, antigen specific T cells are exhausted due to PD-1 inhibitory signals and lack of positive co-stimulation
The binding of GHRH-A (MR409) to GHRH receptor activates the cAMP/PKA signaling pathway, resulting in inhibition of NADPH oxidase activity and dephosphorylation of NFŒ∫B (p65), which leads to the reduction of ROS and IL-6
Ferroptosis is characterized by iron-dependent lipid peroxidation
The various non-canonical p53-modulated cell biological processes that may contribute to tumor suppression are depicted
A network of metabolic pathways that regulate leukemia
The identified pathway between EGFR and JUN for Loi’s breast cancer dataset
The HIF-1Œ± pathway and creation of an HIF-1Œ± knockout mouse model
The active efflux of the chemotherapeutic drugs through ABC transporters plays a major role in cancer cells in resisting chemotherapy
Collectively the data herein support a model whereby ETBF infection triggers a specific relay of cellular interactions initiated by the action of the single bacterial virulence protein, BFT, on CECs that results first in IL-17-producing mucosal immune cells that then turn to act on the CECs to initiate a NFŒ∫B-associated CEC immune response that directs distal colon myeloid mucosal infiltration key to ETBF tumor localization in the distal colon
A working model for Eph receptor function in tumor promotion and tumor suppression
Development of colorectal cancer is driven by genetic alterations in the APC/β-catenin pathway, leading to aberrant Wnt signaling and formation of hyperplastic cryptic foci and early adenomas
Pathway reactivation confers drug resistance by re-engaging index effectors downstream of the drug target, thereby maintaining the original oncogenic signaling output
Pathway bypass confers drug resistance by recruiting alternate effector pathways to sustain the index downstream oncogenic output (for example, transcriptional or translational state)
A. In the absence of Hedgehog ligand (Hh), Patched (Patch) prevents Smoothened (Smo) from entering the primary cilium (PC), repressing Smo activity.
The schematic displays targeting strategies to combat CSCs by blocking stemness signaling pathways
Ca2+ mobilization and Ca2+ removal mechanisms in VSM
Illustration of cross-communication network of BCR, PI3K, and NF-Œ∫B signaling pathways that harbor effective therapeutic targets in lymphoma
Illustration of JAK/STAT signaling pathway that inspires effective therapeutic targets in lymphoma
Overview of apoptosis signaling pathway that contains effective therapeutic targets in lymphoma
Overview of PD-1/PD-Ls signaling pathway that acts as effective therapeutic targets in lymphoma
Molecular targets for therapy in the HH pathway web of collaboration
Genes that are differentially expressed and included in cluster 1, which are up-regulated from 60DG to adult, are denoted by red boxes; genes that are differentially expressed and included in cluster 2, which are down-regulated from 60DG to adult, are denoted by green boxes; genes that are differentially expressed and gene splice variants or gene family members are found in cluster 1 and cluster 2 are denoted by blue boxes; genes that are not differentially expressed are denoted by gray boxes with black lines; and genes that were not detected on the array are denoted by black boxes with white font
(a) Distribution of GLUT1, the main glucose tra... (b) Schematic representation of oxidative phosp... (c) This schematic summarizes glucose metabolis...
After mechanical optic nerve injury (ONC) distinct injury signaling pathways appear to control somal (proximal to the site of injury) and axonal (distal to the site of injury) degeneration
Proposed model of an energy balance-responsive network associated with DNMT1 regulation, DNA methylation and transcriptional regulation of ERŒ± and ERβ
A complex network of pathways regulate mitochondrial biogenesis
Schematic showing the role of Nm23-H1 in cell cycle regulation and apoptosis
The classic pathway involves generation of NO through L-arginine
Hyperglycemia enriches metabolic flux to glycolysis and five principal branches including the polyol pathway, pentose phosphate pathway (PPP), hexosamine pathway, protein kinase C (PKC) pathway, and advanced glycation end-products (AGE) pathway
Fumarate accumulation, HIF-1Œ± regulation, and glycolysis in renal cells with increased intracellular glucose
Filoviruses inhibit the type I IFN response at multiple steps
We show in normal human astrocytes (NHA) that cocaine treatment increased type I interferon responses in a concentration-dependent manner ()
Pre-clinical and clinical models have indicated that the tumor microenvironment, for example pancreatic stellate cells in the case of pancreatic cancer, p53 status, RAS family status, activation of JAK–STAT and PI3K signaling may all play roles in the determination of autophagy dependence within cancer cells, both in vitro and in patients
Illustration shows a simplified scheme of the BRAF/MEK/ERK signaling pathway
The top citrullinated proteins for [ref] were up-loaded and analyzed in cytoscape via reactomeFI
Pathway enrichment analysis of primary human lung cell secretory proteins with decreased abundance in response to PC
Mechanisms of Action of Targeted Therapies in Metastatic Renal Cell Carcinoma
Role of Ras pathway proteins in exo-some biogenesis, cargo selection and release
Viral invasion into the cells leads to the appearance of viral RNA fragments in cytosol, which are detected by RLR monomers
pRB/E2F pathway dysregulation leading to unrestricted CASP3 gene transcription
Activation of PC-3 by PAC-1 and its derivatives via chelation of labile inhibitory zinc
Genomic alterations are often heterogeneous across patients with metastatic castration-resistant prostate cancer (mCRPC)
Genomic alterations involving the PTEN-PI3K-AKT pathway occur in ~50pct of metastatic castration-resistant prostate cancers (mCRPCs) resulting in PI3K-AKT pathway activation
Germline or somatic mutations involving DNA repair genes, such as BRCA1, BRCA2, ATM and MSH2 are present in 20pct of metastatic castration-resistant prostate cancers (mCRPCs)
Cell cycle machinery is governed by cyclins and cyclin-dependent kinases (CDKs) at different phases
Lineage plasticity has been increasingly observed in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor pathway inhibitors (ARPIs) to drive prostate cancer from an adenocarcinoma histology towards a neuroendocrine prostate cancer (NEPC) phenotype
NAD+ biosynthetic and degradative enzymes
a | In the healthy cardiomyocyte, both desmosomes and adherens junctions in the area composita form strong intercellular connections with neighbouring cells
Dysregulation of the complement cascade in C3 glomerulopathy
a, Normal CD34+ stem and progenitor cells preferentially express a short isoform of IRAK4 (IRAK4-S), which promotes stronger activation of MAPK signalling than the NF-Œ∫B pathway
A scheme of the N-linked glycosylation pathway
Proposed mechanism of the suppressive effects of Crabp1 in adipogenesis and adipocyte hypertrophy
The responsive Drosophila intestinal stem cell lineage
Gluconeogenesis, the formation of glucose from non-carbohydrate precursors such as amino acids or lactate, is in part the reversal of glycolysis
Regulatory network hubs are related to neurogenesis
Different bacterial species employ both shared and unique intrinsic mechanisms to destroy cancer
Pathway to chronic rapamycin therapy in prostate cancerModel: Chronic mTORC1 inhibition delays of PCa progression from active surveillance
In host cells, various pattern-recognition receptors (PRRs) recognize viral pathogen-associated molecular patterns (PAMPs), which leads to the activation of transcription factors and the induction of the interferon (IFN) response
Viruses interfere with autophagosome formation and fusion with the lysosome
Tetherin blocks virus release, activates an innate immune response and is counteracted by Vpu or Nef