Cell Signaling

Cell Signaling   Activation of cAMP-dependent protein kinase, PKA G-protein coupled receptors (GPCRs) are one of the largest gene families of signaling proteins. Residing in the plasma membrane with seven transmembrane domains, GPCRs respond to extracellular stimuli that include catecholamine neurotransmitters, neu ... Activation of Csk by cAMP-dependent Protein Kinase Inhibits Signaling through the T Cell Receptor Interaction of T cell receptor with specific antigen in the context of MHC II activates a signal transduction pathway that leads to T cell activation. In the T cell receptor signaling pathway, the src family kinases Lck and Fyn are activated to phos ... Activation of PKC through G protein coupled receptor G-protein coupled receptors (GPCRs) transduce a variety of signals from the extracellular environment across the plasma membrane. One of the common signaling systems utilized by GPCRs activates protein kinase C (PKC), a ubiquitous family of serine/th ... Agrin in Postsynaptic Differentiation The heparan sulphate proteoglycan agrin is well known as the key assembly factor of postsynaptic differentiation at the neuromuscular junction (NMJ), but recent data suggest it also plays a direct role in the organization of the cytoskeleton in the s ... Ahr Signal Transduction Pathway The Ah receptor, bHLH/PAS transcription factor, upon binding of an agonist such as 2,3,7,8-tetrachlorodibenzo-p-dioxin translocates into the nucleus and heterodimerizes with the transcription factor ARNT. The Ahreceptor/ARNT heterodimer binds to diox ... ALK in cardiac myocytes Heart formation is cued by a combination of positive and negative signals from surrounding tissues. Inhibitory signals that block heart formation in anterior paraxial mesoderm include Wnt family members expressed in dorsal neural tube and anti-BMPs ... Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling Ang II binding to AT1-R triggers the activation of Ca2+ signaling and PKC. The signal is then transmitted to the Pyk2 and further to the small G protein Rac1 but not Cdc42, although the direct activation of Rac1 by Pyk2 is not proved in this study. ... Anthrax Toxin Mechanism of Action One of the key causes of anthrax virulence is the production of three specific factors by the gram-positive spore forming bacteria Bacillus anthracis. Even with successful antibiotic treatment, anthrax toxins can remain in the circulation and cause ... ATM Signaling Pathway The ataxia telangiectasia-mutated gene (ATM) encodes a protein kinase that acts as a tumor suppressor. ATM activation by ionizing radiation damage to DNA stimulates DNA repair and blocks progression through the cell cycle. Mutation of the ATM gene ca ... Attenuation of GPCR Signaling The G-protein coupled receptor (GPCR) family transduces extracellular signals across the plasma membrane, activating cellular responses through a variety of second messenger cascades (see PKA and PKC signaling pathways). These receptors provide rapid ... B Cell Survival Pathway Physical interactions between intergrin alpha4beta1 heterodimer expressed on B cells and counter receptors on stroma cells are key mediators of the survival of normal and malignant B cells. Recent data indicate that integrin stimulation increases FBI ... Basic mechanism of action of PPARa, PPARb(d) and PPARg and effects on gene expression Similar to other nuclear hormone receptores, PPAR acts as a ligand activated transcription factor. Upon binding fatty acids or hypolipidemic drugs, PPARa interacts with RXR and regulates the expression of target genes. These genes are involved in the ... BCR Signaling Pathway Significant progress has been made towards delineation of the intrinsic molecular processes that regulate B lymphocyte immune function. Recent observations have provided a clearer picture of the interactive signaling pathways that emanate from the ma ... Bioactive Peptide Induced Signaling Pathway Many different peptides act as signaling molecules, including the proinflammatory peptide bradykinin, the protease enzyme thrombin, and the blood pressure regulating peptide angiotensin. While these three proteins are distinct in their sequence and ... Bone Remodelling Bone density and structure is maintained through a balance of bone resorption by osteoclasts and bone deposition by osteoblasts. The combination of simultaneous resorption and deposition creates continual remodeling of bone while excess osteoclast a ... Ca++/ Calmodulin-dependent Protein Kinase Activation The calcium/calmodulin-dependent kinases (CaMKs) are involved in a large number of cellular responses induced by hormones, neurotransmitters and other signalling. Elevation of calcium functions as a major second messenger, where the intracellular co ... Cadmium induces DNA synthesis and proliferation in macrophages Exposure to divalent cadmium ions (Cd2+) is a known cancer risk factor, but the molecular mechanisms responsible for the inappropriate induction of cellular proliferation by cadmium are still being figured out. One cellular model used to study this ... Calcium Signaling by HBx of Hepatitis B virus Hepatitis B is a small DNA virus that contains only 4 open reading frames in its genome. Three of these ORFs have been identified as the envelope, capsid and polymerase genes, while the function of the fourth has remained unknown until recently. Th ... CARM1 and Regulation of the Estrogen Receptor Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 ass ... CBL mediated ligand-induced downregulation of EGF receptors As with many cell-surface receptors, activation of the EGF receptor can result in receptor internalization through receptor-mediated endocytosis, desensitizing further receptor signaling. This process requires clathrin and occurs in clathrin-coated ... Cell to Cell Adhesion Signaling Interactions between cells responsible for cell to cell adhesion also can communicate signals into the cellular interior, often involving interactions with cytoskeletal elements to produce changes in cell motility, migration, proliferation and shape. ... Ceramide Signaling Pathway Over 1,000 papers and reviews have been written about the role of ceramide in the production of programmed cell death or apoptosis. Ceramide is a sphingosine-based lipid-signaling molecule involved in the regulation of cellular differentiation, prol ... Chaperones modulate interferon Signaling Pathway Signaling by interferon-gamma stimulates anti-viral responses and tumor suppression through the heterodimeric interferon-gamma receptor. Signaling is initiated by binding of interferon-gamma to its receptor, activating the receptor-associated JAK2 t ... Control of skeletal myogenesis by HDAC & calcium/calmodulin-dependent kinase (CaMK) The differentiation of muscle cells is transcriptionally regulated, in part by the myocyte enhancer factor-2, MEF2. During myogenesis MEF2 binds to MyoD and other basic helix-loop-helix factors to activate transcription of genes involved in muscle ce ... Corticosteroids and cardioprotection Myocardial infarction damages heart tissue both during the initial ischemia and the subsequent reperfusion of tissues with oxygen. Corticosteroids can protect cardiac tissue from damage following a heart attack, but the mechanisms by which corticoste ... CXCR4 Signaling Pathway CXCR4 is a chemokine receptor in the GPCR gene family, and is expressed by cells in the immune system and the central nervous system. In response to binding its ligand SDF-1 (stromal cell-derived factor-1), CXCR4 triggers the migration and recruitme ... Cystic fibrosis transmembrane conductance regulator and beta 2 adrenergic receptor pathway The defects in cAMP-regulated chloride channel CTFR are believed to be the major cause for cystic fibrosis. Regulation of CFTR protein by the surface receptor beta adrenergic receptor is mediated through the ezrin/radixin/moesin binding phosphoprotei ... Cytokine Network Several different cell types coordinate their efforts as part of the immune system, including B cells, T cells, macrophages, neutrophils, basophils and eosinophils. Each of these cell types has a distinct role in the immune system, and communicates w ... Cytokines and Inflammatory Response Inflammation is a protective response to infection by the immune system that requires communication between different classes of immune cells to coordinate their actions. Acute inflammation is an important part of the immune response, but chronic ina ... D4-GDI Signaling Pathway D4-GDI (GDP dissociation inhibitor) is a negative regulator of the ras related Rho Family of GTPases. Since the rho GTPases promote cytoskeletal and membrane changes associated with apoptotic cell death, the removal of the D4-GDI block through its cl ... Degradation of the RAR and RXR by the proteasome Once retinoids are bound by the RAR/RXR heterodimer they became transcriptional activated. As a consequence they are degraded by the proteasome. Phosphorylation in the activation domain one (AF1) and presence of the activation domain 2 (AF2) triger t ... Effects of calcineurin in Keratinocyte Differentiation The differentiation of keratinocytes constantly replenishes the upper layers of human skin we lose each day. One factor that contributes to terminal keratinocyte differentiation is increased levels of intracellular calcium. Adding calcium to the me ... EGF Signaling Pathway The epidermal growth factor (EGF) peptide induces cellular proliferation through the EGF receptor, which has a tyrosine kinase cytoplasmic domain, a single transmembrane domain and an extracellular domain involved in EGF binding and receptor dimeriza ... Eph Kinases and ephrins support platelet aggregation Eph kinases are a family of receptor tyrosine kinases with an extracellular domain that binds their ligand, the ephrins, and an intracellular kinase domain. The ephrins are also expressed on the cell surface, so that interaction between Eph kinases a ... EPO Signaling Pathway Erythropoietin functions to increase the number of red blood cells. Thus, it has found utility as a drug for those needing to replenish erythrocytes for a number of reasons. The signaling mechanism includes multimerization of the receptor upon ligand ... Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia Activation of the MAPK kinase pathway has been identified as a mechanism that integrins use to regulate gene expression leading to cell shape changes during cell spreading or migration Epithelial cells respond to extracellular matrix (ECM) cause inte ... Erk1/Erk2 Mapk Signaling pathway The p44/42 MAP Kinase pathway consists of a protein kinase cascade linking growth and differentiation signals with transcription in the nucleus. Growth factor receptors and tyrosine kinases activate Ras which in turn activates c-Raf, MEK, and MAP kin ... Erythropoietin mediated neuroprotection through NF-kB Erythropoietin (Epo) is most commonly known as the cytokine secreted by the kidneys that stimulates red blood cell production and is used as a drug for the treatment of anemias. Epo is also secreted in the brain in response to hypoxia, such as ische ... Eukaryotic protein translation The scanning translation initiation model suggests that 40S ribosomal subunit preloaded with factors bind to the 5’ end of the mRNA near the cap. The 48S subunit moves along the mRNA until it finds the initiation triplet and in complex with tRNA and ... FAS signaling pathway ( CD95 ) Receptors in the TNF receptor family are associated with the induction of apoptosis, as well as inflammatory signaling. The Fas receptor (CD95) mediates apoptotic signaling by Fas-ligand expressed on the surface of other cells. The Fas-FasL interacti ... Fc Epsilon Receptor I Signaling in Mast Cells The Fc Epsilon Receptor 1 signaling pathway in mast cells uses multiple core signal path to achieve its necessary ends. Through the BTK protein and PKC Mast cells are able to degranulate, through the PKC and MAPK paths the cells are able to alter cyt ... fMLP induced chemokine gene expression in HMC-1 cells Neutrophils respond to bacterial infection by releasing reactive oxygen species that kill bacteria and by expressing chemokines that attract other immune cells to the site of infection. The multisubunit enzyme NADPH oxidase expressed by neutrophils ... G-Protein Signaling Through Tubby Proteins The tubby gene product is expressed in the brain and has been implicated by mouse genetics in obesity and other disorders such as blindness. Structural analysis predicted that this gene acts as a transcription factor, binding to DNA to regulate gene ... Growth Hormone Signaling Pathway Growth hormone plays a major role in regulating growth during childhood and adolescence and also regulates metabolism. Defects in growth hormone signaling can result in dwarfism and decreases in growth hormone levels with age have been suggested to p ... g-Secretase mediated ErbB4 Signaling Pathway The HER4/erbB4 receptor tyrosine kinase is a member of the EGF1 receptor family. HER4 is a receptor for the neuregulins (NRGs), a family of growth and differentiation factors. HER4 can also bind and be activated by heparin-binding EGF growth factor, ... How Progesterone Initiates the Oocyte Maturation Progesterone (Pg) binds to both intracellular iPR and plasma membrane– bound mPR. (Right Top) After binding to Pg, iPR is recruited to the membrane associated protein tyrosine kinase p60c- src, which induces activation of the MAPK signaling pathway. ... Human Cytomegalovirus and Map Kinase Pathways To replicate in the host cell, viruses commandeer cellular signaling pathways. Cytomegalovirus (CMV) is a DNA virus with that is widespread in the population but usually causes disease only in immunocompromised individuals and is also a viral cause o ... Hypoxia-Inducible Factor in the Cardiovascular System Hypoxia (or low O2 levels) affects various pathologies. First, tissue ischemia, a variation in O2 tension caused by hypoxia/reoxygenation, can lead to endothelial cell changes. For example, long periods of ischemia result in endothelial changes, such ... IFN alpha signaling pathway Interferon alpha plays a role in viral infections. Signaling takes place through an IFN Recpetor complex consisting of two alpha chains (Type I receptor) complexed with Jak1 and Tyk2. These kinases phosphorylate Stat1 and Stat2 respectively. IFN gamma signaling pathway Interferon gamma is secreted from CD4+ Th1 cells, CD8 cells, gamma/delta T cells and activated NK cells. It plays a role in activating lymphocytes to enhance anti-microbial and anti-tumor effects. In addition it plays a role in regulating the prolife ... IGF-1 Signaling Pathway Insulin like growth factor 1 (IGF-1) and its receptor (IGF-1R) provide a potent proliferative signaling system that stimulates growth in many different cell types and blocks apoptosis. In vivo IGF-1 acts as an intermediate of many growth hormone resp ... IL 17 Signaling Pathway Inflammation is a complex response involving many different cells and signaling molecules, including the secretion of the cytokine IL-17 by activated T cells. IL-17 secretion is restricted to specific subsets of T cells but the receptor for IL-17 is ... IL 18 Signaling Pathway IL-18 is a pro-inflammatory cytokine similar in structure and mechanism of action to IL-1 beta. Formation of active IL-18 by macrophages requires cleavage of an inactive precursor by caspase-1 protease, also termed the IL-1 converting enzyme (ICE). O ... IL 2 signaling pathway Interleukin 2 (IL-2) is a potent cytokine that can lead to cellular activation and proliferation. IL-2 Receptors are found on activated B-Cells, LPS treated Monocytes, and many T cells. The receptor is formed from three chains alpha (CD25), beta (CD1 ... IL 3 signaling pathway Interleukin-3 promotes the proliferation and differentiation of hematopoietic cells through binding to its receptor. The receptor for IL-3 is a heterodimer with a ligand-specific alpha chain (70 kD, CD123) and a common beta chain (shared with IL-5 an ... IL 4 signaling pathway Interleukin 4 (IL-4) is a cytokine that can lead to development of Th2 cells. The 140 kD IL-4 Receptor (CD124) is found on many cell types, even those of non-hematopoietic origen. The receptor is formed from two chains: IL-4R(alpha) and the IL-2R gam ... IL 5 Signaling Pathway IL-5 is an inflammatory signaling molecule that primarily stimulates eosinophil proliferation, maturation and activation. Eosinophils are leukocytes involved in inflammatory responses that defend against parasites and cause some aspects of asthma, al ... IL 6 signaling pathway Interleukin-6 (IL-6) is a cytokine that provokes a broad range of cellular and physiological responses. In addition to playing a role in inflammation and hematopoiesis, IL-6 is involved in other processes such as neuronal differentiation and bone los ... IL-10 Anti-inflammatory Signaling Pathway IL-10 is a cytokine with potent anti-inflammatory properties, repressing the expression of inflammatory cytokines such as TNF-alpha, IL-6 and IL-1 by activated macrophages. The IL-10 receptor is in the JAK/STAT class of receptors but activation of t ... IL12 and Stat4 Dependent Signaling Pathway in Th1 Development Interleukin-12 (IL-12) promotes cell-mediated immunity by inducing Th1 cell differentiation and activation of both T cells and NK cells. Dendritic cells and macrophages in peripheral tissues act as antigen presenting cells and secrete IL-12 as one c ... IL-2 Receptor Beta Chain in T cell Activation The IL-2 receptor is a key component of immune signaling and is required for the activation, proliferation, and survival of T cells. This receptor is composed of three polypeptide chains, the alpha, beta and gamma chains. The IL-2 receptor gamma ch ... IL22 Soluble Receptor Signaling Pathway IL-22 is an inflammatory cytokine related to IL-10 that is produced by T cells and that induces a response in cells through a heterodimeric cell surface receptor composed of IL-22R1 and IL-10R2C. One of the actions of IL-22 appears to be the inducti ... IL-7 Signal Transduction IL-7 is a key cytokine in the immune system, essential for normal development of B cells and T cells. Mice with the IL-7 receptor deleted lack B and T cells. Some humans with SCID (severe combined immunodeficiency disease) also have mutation of the ... Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages Lipopolysaccharide (LPS) from XX bacteria induces a wide range of inflammatory responses, including the response of alveolar macrophages to bacteria in the lungs. CD14 and the Toll-like receptor TLR4 are activated by LPS, initiating a signaling casc ... Influence of Ras and Rho proteins on G1 to S Transition The cell cycle transition from G1 to S phase is a key regulatory point in the cell cycle. This transition is regulated by the checkpoint kinase cdk2 that activates the G1 to S transition when it is associated with cyclin E. Cdk2/Cyclin E causes the ... Inhibition of Cellular Proliferation by Gleevec The drug Gleevec (also known as imatinib mesylate or STI-571) was approved by the FDA in 2001 for the treatment of CML, chronic myeloid leukemia. While traditional cytotoxic cancer treatments such as chemotherapy or radiation therapy kill all dividi ... Insulin Signaling Pathway The appropriate signaling through the insulin pathway is critical for the regulation of glucose levels and the avoidance of diabetes. Insulin forms a complex with the Insulin Receptor (IR) and b chains to form the active signaling complex. Through re ... Integrin Signaling Pathway Integrins are cell surface receptors that interact with the extracellular matrix and mediate intracellular signals in response to the extracellular matrix including cellular shape, mobility, and progression through the cell cycle. Integrins do not th ... Ion Channel and Phorbal Esters Signaling Pathway Molecules transmitting signals into cells often act through receptors in the plasma membrane that stimulate production of second messengers. When activated by a plasma membrane receptor, the enzyme phospholipase C (PLCg) hydrolyzes the membrane lipid ... Ion Channels and Their Functional Role in Vascular Endothelium Endothelial cells (EC) form a multifunctional signal-transducing surface that performs different tasks dependent on its localization in the vessel tree. Arterial EC provide a pathway for delivery of oxygen from blood to tissue. They modulate the tone ... Keratinocyte Differentiation The epidermis, which provides a protective barrier that undergoes a constant renewal, is a multi-layered tissue with the proliferating cells located in the basal layer. As cells leave the basal layer the underog significant differentiation, biochemi ... Lck and Fyn tyrosine kinases in initiation of TCR Activation T cell activation is initiated by recognition of antigen by the T cell receptor (TCR) in the context of Class II MHC on an antigen-presenting cell. The T cell receptor contains multiple subunits and interacts with several factors to transduce antigen ... Links between Pyk2 and Map Kinases This diagram is a compilation of Pyk2 effort cascades. In specific cell types the receptor and effoectors will vary. Binding of a transmembrane receptor triggers the activation of Ca2+ signaling and PKC. The signal is then transmitted to Pyk2 and ... Map Kinase Inactivation of SMRT Corepressor Corepressors are coregulators that interact with transcriptional silencers in a variety of pathways such as cell proliferation, differentiation and apoptosis. Abnormal corepressor-silencer interactions have been implicated in a variety of human dise ... MAPKinase Signaling Pathway The ever evolving mitogen-activated protein kinase (MAP kinase) pathways consist of four major groupings and numerous related proteins which constitute interrelated signal transduction cascades activated by stimuli such as growth factors, stress, cyt ... mCalpain and friends in Cell motility The mammalian calpain gene family currently contains 13 distinct large subunit products most of which complex with one of two smaller 30kDa subunits. ( An excellent introduction to the calpain family can be found on a web site created by Valery Thomp ... Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) The most recognized mechanism by which peroxisome proliferators regulated gene expresssion is through a PPAR/RXR heterodimeric complex binding to a peroxisome proliferator-response element (PPRE) (classical mechanism). However, there are the possibil ... Meiotic Arrest in Oogenesis Mammalian oogenesis is marked by a prolonged pause in meiosis II that can last many years for human oocytes. This meiotic arrest is not released to complete meiosis until after fertilization, at which time the second polar body is released, and the ... Melanocyte Development and Pigmentation Pathway Studies with homozygous knockout mice have suggested that stem cell factor (SCF or KITLG), c-Kit, microphthalmia (Mitf), and B-cell CLL/lymphoma 2 (Bcl2) genes regulates melanocytic development. The SCF activation of Kit receptor leads to Mitf phosp ... Msp/Ron Receptor Signaling Pathway MSP, macrophage-stimulating protein, acts through the transmembrane receptor kinase RON (Stk in mice) to play a role in inflammation and the response to tissue injury. MSP is secreted by the liver into the blood as pro-MSP, an inactive precursor form ... mTOR Signaling Pathway mTOR (mammalian target of rapamycin) appears to play a central role in signaling caused by nutrients and mitogens such as growth factors to regulate translation. The drug rapamycin acts on mammalian cells through the mTOR protein kinase, also known ... Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation IGF-1R, the type 1 receptor for insulin-like growth factor, mediates cell survival and growth in response to its ligands IGF-1 and IGF-2. This tyrosine kinase receptor is widely expressed in many cell types and is a key mediator of growth. Overexpr ... Nerve growth factor pathway (NGF) Nerve growth factor (NGF) is one of a family of neurotrophins that induce the survival and proliferation of neurons. In cell culture NGF induces the formation of neurite projections and in vivo may stimulate the innervation of tissues. NGF plays a ... Neuropeptides VIP and PACAP inhibit the apoptosis of activated T cells Vasoactive intestinal peptide (VIP) and the structurally related pituitary adenylate cyclase-activating polypeptide (PACAP), two neuropeptides present in the lymphoid microenvironment, elicit a broad spectrum of biological functions, including the mo ... Neuroregulin receptor degredation protein-1 Controls ErbB3 receptor recycling The neuregulins comprise a subfamily of at least four epidermal growth factor (EGF)-like growth factors that influence a variety of cellular events, including proliferation, differentiation, migration, survival, and fate. The most thoroughly examined ... NFAT and Hypertrophy of the heart (Transcription in the broken heart) Hypertrophy associated with both hypertension and obstruction to ventricular outflow leads to pathologic cardiac growth and it is associated with increase morbidity and mortality. Symptomatic ventricular disease takes a growing toll on the health of ... NFkB activation by Nontypeable Hemophilus influenzae The role of Hemophilus influenzae in ear infections and chronic obstructive pulmonary disease includes the induction of an inflammatory response through activation of the transcription factor NF-kB. In addition to activation of inflammatory cytokine ... NF-kB Signaling Pathway Nuclear factor kB (NF-kB) is a nuclear transcription factor that regulates expression of a large number of genes that are critical for the regulation of apoptosis, viral replication, tumorigenesis, inflammation, and various autoimmune diseases. The a ... Nitric Oxide Signaling Pathway Glutamatergic-mediated nitric oxide (NO) production occurs via the N-methyl-D-aspartic acid (NMDA) postsynaptic density protein 95 (PSD95)-neuronal nitric oxide synthase (NOS1) ternary complex. The increased intracellular Ca2+ stimulates the interact ... Nitric Oxide Signaling Pathway Glutamatergic-mediated nitric oxide (NO) production occurs via the N-methyl-D-aspartic acid (NMDA) postsynaptic density protein 95 (PSD95)-neuronal nitric oxide synthase (NOS1) ternary complex. The increased intracellular Ca2+ stimulates the interact ... Nitrogen-depedent regulation of Rtg1 and Rtg3 in TOR pathway Many key signaling molecules are conserved from yeast to man. mTOR is a protein kinase involved in nutrient and growth factor signaling in humans that has a yeast homolog with a similar role, TOR1. Like its human counterpart, yeast TOR1 is also inh ... NO2-dependent IL 12 Pathway in NK cells Macrophages and NK cells help provide innate immunity against infection by intracellular parasites and communicate with each other to regulate this process. When stimulated, macrophages secrete the cytokine IL-12 that is essential for activation of ... <