• In addition to these domains, LNK possesses a proline-rich region that contains a minimal consensus sequence of Pro-X-X-Pro, which is recognized by the SH3 domain of another protein, as well as putative tyrosine phosphorylation motifs. (wikipedia.org)
  • Regulates neutrophil polarization by regulating AKT1 phosphorylation through a mechanism that is independent of PIK3CG activity (By similarity). (nih.gov)
  • Signaling through the insulin receptor occurs through an intracellular tyrosine kinase domain and resultant phosphorylation of the receptor, itself, and downstream effector and scaffolding proteins. (nih.gov)
  • Dimerization of SRC Kinase Adaptor Phosphoprotein 2 (SKAP2) induces an increase of binding for most SRC kinases suggesting a fine-tuning with trans-phosphorylation for kinase activation. (bvsalud.org)
  • By combining a luciferase complementation assay and extensive site-directed mutagenesis, we demonstrated that SKAP2 interacts with SRC kinases through a modular organization depending both on their phosphorylation-dependent activation and subcellular localization. (bvsalud.org)
  • In this article, we show that a modular architecture of SKAP2 drives its interaction with SRC kinases, with the binding capacity of each module depending on both their localization and phosphorylation state activation. (bvsalud.org)
  • High levels of tyrosine phosphorylation correspond to enhanced proliferative state ( N Engl J Med 353(2) (2005)">3 ). (cancerdiagnosisprognosis.org)
  • 5. Hyperosmotic stress induces rapid focal adhesion kinase phosphorylation at tyrosines 397 and 577. (nih.gov)
  • 7. Integrin-mediated cell adhesion promotes tyrosine phosphorylation of p130Cas, a Src homology 3-containing molecule having multiple Src homology 2-binding motifs. (nih.gov)
  • 9. The integrin beta1 subunit transmembrane domain regulates phosphatidylinositol 3-kinase-dependent tyrosine phosphorylation of Crk-associated substrate. (nih.gov)
  • 13. Induced focal adhesion kinase (FAK) expression in FAK-null cells enhances cell spreading and migration requiring both auto- and activation loop phosphorylation sites and inhibits adhesion-dependent tyrosine phosphorylation of Pyk2. (nih.gov)
  • 14. Dissociation of FAK/p130(CAS)/c-Src complex during mitosis: role of mitosis-specific serine phosphorylation of FAK. (nih.gov)
  • 16. Mechanisms of CAS substrate domain tyrosine phosphorylation by FAK and Src. (nih.gov)
  • We aimed to study the molecular mechanisms of how the gastric pathogen Helicobacter pylori hijacks cortactin phosphorylation via tyrosine kinase Abl to trigger cancer-related signal transduction events. (mdpi.com)
  • We have previously shown that trivalent metabolites of iAs, arsenite (iAs III ) and methylarsonous acid (MAs III ) inhibit insulin-stimulated glucose uptake (ISGU) in 3T3-L1 adipocytes by suppressing the insulin-dependent phosphorylation of protein kinase B (PKB/Akt). (nih.gov)
  • Our goal was to identify the molecular mechanisms responsible for the suppression of PKB/Akt phosphorylation by iAs III and MAs III . (nih.gov)
  • Subtoxic concentrations of iAs III or MAs III had little or no effect on the activity of phosphatidylinositol 3-kinase (PI-3K), which synthesizes phosphatidylinositol-3,4,5-triphosphate (PIP 3 ), or on phosphorylation of PTEN (phosphatase and tensin homolog deleted on chromosome ten), a PIP 3 phosphatase. (nih.gov)
  • Neither iAs III nor MAs III interfered with the phosphorylation of 3-phosphoinositide-dependent kinase-1 (PDK-1) located downstream from PI-3K. (nih.gov)
  • It is known that the human Ras GTPase activating protein (GAP) p120-GAP can be phosphorylated by different members of the Src kinase family and recently phosphorylation of the GDP/GTP exchange factor (GEF) CDC25Mm/GRF1 by proteins of the Src kinase family has been revealed in vivo [Kiyono, M., Kaziro, Y. & Satoh, T. (2000) J. Biol. (embl.de)
  • The use of the catalytic domain of p60c-Src showed that its SH3/SH2 domains are not required for the interaction and the phosphorylation of both regulators. (embl.de)
  • The phosphorylation of p120-GAP by p60c-Src inhibited its ability to stimulate the Ha-Ras-GTPase activity, whereas phosphorylation by Lck did not display any effect. (embl.de)
  • phosphorylation by Lck increased its capacity to stimulate the GDP/GTP exchange on Ha-Ras, whereas its phosphorylation by p60c-Src was ineffective. (embl.de)
  • Our results suggest that phosphorylation by p60c-Src and Lck is a selective process that can modulate the activity of p120-GAP and CDC25Mm towards Ras proteins. (embl.de)
  • [ 3 ] The activity of MAPKs is regulated through phosphorylation by MAPK kinases (MAPKKs), which in turn are regulated by MAPKK kinases (MAPKKKs). (medscape.com)
  • The subsequent step involves phosphorylation by this activated tyrosine kinase of other molecules, STATs which is an abbreviation for S ignal T ransducers and A ctivators of T ranscription in the cell nucleus). (pharmacology2000.com)
  • Following STAT phosphorylation by JAK, the phosphorylated STAT monomers bind to a special structural region, the SH2 domain, located on another STAT monomer. (pharmacology2000.com)
  • Using specific kinase inhibitors, we demonstrate that tyrosine phosphorylation of Tks5 is catalyzed by Src tyrosine kinase. (biomedcentral.com)
  • In addition, treatment of cells with LY294002, an inhibitor of PI 3-kinase, or mutation of the PX domain reduces tyrosine phosphorylation and membrane translocation of Tks5. (biomedcentral.com)
  • The phosphorylation of Akt is mediated by the PI3 kinase pathway while that of CREB is dependent on the activation of both MAPK kinase and p38 MAPK. (biomedcentral.com)
  • Survival assays with various kinase inhibitors suggested that the activation/phosphorylation of both Akt and CREB contributes to IGF-1 mediated cell survival in PC12 cells. (biomedcentral.com)
  • The binding of the ligand to the receptor triggers the oligomerisation of the receptors and phosphorylation of specific tyrosine residues in the intracytoplasmic kinase domain. (eonco.info)
  • The activated GTP-bound form of Ras then starts a kinase cascade composed of Raf, MAPKK, and MAPK leading to phosphorylation of prooncogene Jun on serine and threonine residues to induce transcriptional activation. (yale.edu)
  • Insulin signaling is initiated by binding of insulin to the insulin receptor (IR) tyrosine kinase, which results in IR activation through autophosphorylation on tyrosine residues and then tyrosine phosphorylation of insulin receptor substrates (IRSs) such as IRS-1. (biomedcentral.com)
  • Tyrosine phosphorylation of RNA polymerase II carboxyl-terminal domain by the Abl-related gene product. (nih.gov)
  • Tyrosine phosphorylation of mammalian RNA polymerase II carboxyterminal domain. (nih.gov)
  • Inhibition of DNA binding by the phosphorylation of poly ADP-ribose polymerase protein catalysed by protein kinase C. Biochem Biophys Res Commun 187 , 730-736. (nih.gov)
  • Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. (nih.gov)
  • Ligand binding dimerises the receptors and activates their intracellular tyrosine kinase domains, resulting in phosphorylation of tyrosine residues acting as docking sites for intracellular signalling molecules. (smw.ch)
  • BTK has two critical tyrosine phosphorylation sites, Y223 in the SH3 domain and Y551 in the kinase domain. (biomedcentral.com)
  • Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. (lookformedical.com)
  • They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES , which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES). (lookformedical.com)
  • Our data indicate a direct role for TEL-AML1, via increasing the activity of RAC1, in regulating the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which results in transcriptional induction of MYC. (ashpublications.org)
  • The SH2 domain spans approximately 100 amino acid residues and binds phosphotyrosine-containing proteins such as kinases. (wikipedia.org)
  • This motif is responsible for facilitating the homo- or heterodimerization of SH2-B family proteins as a mechanism for regulating signal transduction. (wikipedia.org)
  • Engagement of the B-cell antigen receptor (BCR) activates kinases of the Src and Syk families and signaling complexes assembled by adaptor proteins, which dictate B-cell fate and function. (nih.gov)
  • The interaction between 3BP2 and Vav proteins involved both constitutive and inducible mechanisms. (nih.gov)
  • This gene encodes the prototype of the membrane-associated guanylate kinase (MAGUK) family proteins. (nih.gov)
  • These may include scaffolding proteins such as the Insulin Receptor Substrate (IRS) 1- 4, other proteins containing src-homology domains (SH2/3), protein tyrosine phosphatases such as PTB-1B, and others. (nih.gov)
  • As an example, Pim-1 serine/threonine kinase (PIM1) regulates cell proliferation and survival that might lead to reduction of therapeutic drug efficacy by promoting the Janus kinases/signal transducer and activator of transcription proteins (JAK/STAT) signaling pathway in MYC proto-oncogene (MYC)-driven cancer ( Nat Rev Cancer 11(1) (2011)">13 - Mol Cancer Ther 9(9) (2010)">16 ), particularly in breast cancer. (cancerdiagnosisprognosis.org)
  • In addition to active Ras proteins, several interac- tion partners have been identified, including Rab5,7 ABL tyrosine kinases,8 signal-transducing adapter molecule,9 epidermal growth factor receptor (EGFR),10 and 14-3-3 proteins.11 Two downstream RIN1 effector pathways have been described. (malt1inhibitor.com)
  • In addition to its association with Ras, GAP has been shown to bind to several tyrosine-phosphorylated proteins in cells stimulated by growth factors or expressing transforming tyrosine kinase variants. (embl.de)
  • Cloning of the chicken and quail genes encoding the putative receptor for RSV, subgroup A. Although the sequencing of genes encoding this long-sought receptor is not yet complete, it will undoubtedly offer a new perspective on viral-host interactions, the mechanism of early events in the virus life cycle, and the nature of the presumptively polymorphic avian proteins that recognize the several subgroups of RSV. (nih.gov)
  • Characterization of src mutants with host-dependent and dominant-negative phenotypes that define important functional domains outside the protein-tyrosine kinase domain of sre proteins (15, 16, 17, 18). (nih.gov)
  • In conjunction with work in several other labs, these mutants brought the Src-homology (SH) domains 2 and 3 to widespread attention, providing new opportunites for identifying the proteins that are crucial modifiers and targets for Sre-like kinases. (nih.gov)
  • BCL2 family of proteins is the hallmark of apoptosis regulation. (hindawi.com)
  • The mechanism of apoptosis is evolutionarily conserved and is executed by a family of proteins, called caspases. (hindawi.com)
  • their activation is mainly regulated by the BCL2 family proteins [ 2 - 4 ]. (hindawi.com)
  • The first, which is called the intrinsic cell death pathway, is evoked by intracellular stresses like radiation, growth factor withdrawal, cytokine deprivation, cytotoxic drugs and is regulated by BCL2 family proteins [ 6 , 7 ]. (hindawi.com)
  • This pathway is activated by the cell-surface death receptors CD95 (Apo-1 or Fas)/TRAIL/tumor necrosis factor (TNF) receptor 1 family proteins which are located on the plasma membrane, and directly activates the caspase cascade via the recruitment of the "initiator" caspase-8 within a death-inducing signaling complex (DISC) [ 8 ]. (hindawi.com)
  • This domain is found in many signal-transducing proteins 25 . (pharmacology2000.com)
  • The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. (biomedcentral.com)
  • No significant homology exists between CD19 and other known proteins, making it an ideal biomarker for B-cells. (shu.edu)
  • Current research goals in the lab relate to the spatio-temporal coordination of FGF2 secretion in living cells, the analysis of the molecular mechanism by which FGF2 physically traverses the plasma membrane and the relevance of this process for other unconventional secretory proteins such as HIV Tat. (db-engine.de)
  • Neurotrophic tropomyosin receptor kinase ( NTRK ) gene rearrangements have recently emerged as targets for cancer therapy, because novel compounds have been developed that are selective inhibitors of the constitutively active fusion proteins that arise from these molecular alterations. (eonco.info)
  • The Trk receptor family comprises three transmembrane proteins referred to as Trk A, B and C (TrkA, TrkB and TrkC) receptors, and are encoded by the NTRK1 , NTRK2 and NTRK3 genes , respectively. (eonco.info)
  • There are 18332 RasGEF domains in 18317 proteins in SMART's nrdb database. (embl.de)
  • Taxonomic distribution of proteins containing RasGEF domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with RasGEF domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing RasGEF domain in the selected taxonomic class. (embl.de)
  • We are using biochemical and genetic approaches as well as X-ray crystallography to determine the mechanism of activation of receptor tyrosine kinases, how they recruit target proteins, and the mode of action of downstream signaling proteins in normal cellular processes and in diseases caused by dysfunctional receptor tyrosine kinases. (yale.edu)
  • Receptor tyrosine kinases undergo ligand-dependent dimerization, which activates their intrinsic protein tyrosine kinase activity resulting in autophosphorylation and subsequent interaction and recruitment of multiple cellular target proteins. (yale.edu)
  • Many signaling proteins carry SH2 domains plus one or more small protein modules such as SH3, PH, PTB, WW or FYVE domains. (yale.edu)
  • In addition to direct recruitment by RTKs, many signaling proteins are recruited by an alternative mechanism involving a family of membrane linked docking proteins such as FRS-2a, and b, IRS-1 and 2, and Gab-1 and 2, among many others. (yale.edu)
  • Sialic acid-binding immunoglobulin-like lectins (Siglecs) belong to a family of transmembrane proteins able to dampen host immune responses and set appropriate immune activation thresholds upon ligation with their natural ligands, the sialylated carbohydrates. (frontiersin.org)
  • Siglecs belong to a family of transmembrane proteins that display a variable numbers of C2-set immunoglobulin domains (from 1 in CD33 to 16 in Siglec-1), an amino-terminal V-set immunoglobulin domain that recognizes sialic acid residues ( 1 - 3 ) and a conserved arginine residue that binds carbohydrates. (frontiersin.org)
  • BACKGROUND: &Aims: Src homology and collagen (Shc) proteins are major adapters to extra-cellular signals however the regulatory role of Shc isoforms in sterile inflammatory responses in alcoholic hepatitis (AH) has not been fully investigated. (stanford.edu)
  • HN - 2017 MH - ADAM12 Protein UI - D000072199 MN - D8.811.277.656.675.374.102.125 MN - D9.400.430.500.125 MN - D12.776.395.33.125 MS - A disintegrin and metalloproteinase domain-containing protein that is expressed as two alternatively-spliced forms: a long transmembrane form (ADAM12-L) and a short soluble form (ADAM12-S). It modulates the cleavage of INSULIN-LIKE GROWTH FACTOR BINDING PROTEINS and may also regulate CELL FUSION during MYOGENESIS. (nih.gov)
  • The intricate equilibrium of phosphotyrosine residues in proteins is controlled by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) 4 , 5 . (cancerbiomed.org)
  • LNK contains 3 functional domains: a C-terminal Src homology 2 (SH2) domain, a pleckstrin homology (PH) domain, and a dimerization domain. (wikipedia.org)
  • SKAP2 contains three interacting modules consisting in the dimerization (DIM) domain, the SRC homology 3 (SH3) domain, and the second inter-domain located between the pleckstrin homology (PH) and the SH3 domains. (bvsalud.org)
  • The NH2-terminal region of Sos contains a Dbl homology (DH) domain in tandem with a pleckstrin homology (PH) domain. (embl.de)
  • In the case of AKT,the interaction domain pleckstrin homology AKT membrane PIP3 bound conformation gives PDK1 Change to phosphorylate PDK1 AKT AKT erm Glicht the 308th threonine Although the r Many people the PDK1 substrates remain to be defined, the oncogenic activity t of aberrant PI3K Pathway in PDK1 AKT has been widely validated. (atpasepathway.com)
  • The PH domain spans approximately 120 amino acid residues and binds the phosphatidylinositol lipids found in the cell membrane. (wikipedia.org)
  • In this chapter, we will focus on molecular events leading to GLUT4 translocation, starting with activation of insulin receptors through signaling cascade involving phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) and finally, the action of their effectors. (intechopen.com)
  • The phosphatidylinositol 3-kinase (PI3K) pathway is frequently deregulated in human cancer and is an essential regulator of cellular proliferation. (cancerdiagnosisprognosis.org)
  • The phosphatidylinositol 3-kinase (PI3K) pathway is one of the most activated signaling pathways in human cancer. (cancerdiagnosisprognosis.org)
  • We found that it is a phosphatidylinositol (3,4,5)-trisphosphate-dependent Arf6 GAP that binds RhoA-GTP but lacks RhoGAP activity. (biologists.com)
  • We aimed to determine which tyrosine kinases contribute to resistance elicited by PI3K silencing and inhibition. (cancerdiagnosisprognosis.org)
  • Results: Activated zeta chain of T-cell receptor-associated protein kinase 70 (ZAP70) generated resistance to PI3K inhibition. (cancerdiagnosisprognosis.org)
  • Upon activation of receptor tyrosine kinases (RTKs), recruitment of PI3K to the cell membrane occurs via coupling the Src homology-2 (SH2) domains of p85 with tyrosine phosphorylated residues of activated receptors ( Nat Rev Drug Discov 8(8) (2009)">4 ). (cancerdiagnosisprognosis.org)
  • Oncogenic RAS and other tyrosine kinases can cause PI3K activation. (cancerdiagnosisprognosis.org)
  • Previous studies have identified the contribution of several activated tyrosine or serine/threonine kinases to growth compensation upon PI3K inhibition ( Otorhinolaryngol Head Neck Surg 1(2) (2016)">8 - Oncogene 30(22) (2011)">10 ). (cancerdiagnosisprognosis.org)
  • In addition to this, pharmacological inhibition of the PI3K pathway in cancer cells leads to up-regulation of receptor tyrosine kinases through feedback loops that circumvent baseline level of PI3K inactivation. (cancerdiagnosisprognosis.org)
  • Elucidation of the primary mechanisms of PI3K resistance might be a significant therapeutic approach for tumorigenesis ( Mol Cancer 18(1) (2019)">6 ). (cancerdiagnosisprognosis.org)
  • Upon BCR activation, CD19 also enhances BCR-induced signaling crucial for B cell expansion, through recruitment and activation of PI3K and downstream Akt kinases. (shu.edu)
  • Activation of the PI3K/Akt pathway mediates crucial cellular functions regulated by receptor tyrosine kinases, such as cell growth, proliferation, survival and metabolism. (biomedcentral.com)
  • Previously, we reported that the whole-body knockout of the Src homology domain-containing adaptor protein Nck1 improves overall glucose homeostasis and insulin-induced activation of the PI3K/Akt pathway in liver of obese mice. (biomedcentral.com)
  • Here, we demonstrate that Nck1 regulates the activation of the PI3K/Akt pathway in a protein tyrosine phosphatase 1B (PTP1B)-dependent mechanism. (biomedcentral.com)
  • Activation of Akt involves PI3K, which converts PIP2 to PIP3 following its interaction with receptor tyrosine kinases (RTKs) or tyrosine-phosphorylated (pY) substrates of RTKs [ 2 ]. (biomedcentral.com)
  • These compensatory mechanisms include forkhead box O (FOXO) transcription factors along with mitogen-activated protein kinase (MAPK)-dependent pathways ( Cancer Discov 9(4) (2019)">11 , Cancer Cell 21(2) (2012)">12 ). (cancerdiagnosisprognosis.org)
  • The Ras family of GTPases is a collection of molecular switches that link receptors on the plasma membrane to signaling pathways that regulate cell proliferation and differentiation. (embl.de)
  • The MAPK, Syk kinase, NF-κB and JAK/STAT intracellular signalling pathways are triggered by cytokines bound to their receptors. (medscape.com)
  • BCL2 protein family, through its role in regulation of apoptotic pathways, is possibly related to cancer pathophysiology and resistance to conventional chemotherapy. (hindawi.com)
  • IGF-1 plays anti-apoptotic and other functions by activating multiple signaling pathways including Akt kinase, a serine/threonine kinase essential for cell survival. (biomedcentral.com)
  • These results reveal a potential mechanism for coupling of Ras and Rac signaling pathways. (embl.de)
  • Various diseases are caused by dysfunctions in receptor tyrosine kinases or in critical components of signaling pathways that are activated by receptors tyrosine kinases. (yale.edu)
  • There are three subfamilies of MAPKs, each comprising several interactive kinase cascades: c-Jun N-terminal kinase (JNK), extracellular signal-related kinase (ERK) and p38 MAPK. (medscape.com)
  • The binding of TrkA receptor by NGF causes the activation of the Ras/Mitogen activated protein kinase (MAPK) pathway, which leads to increased proliferation and cellular growth through extracellular signal-regulated kinase (ERK) signalling. (eonco.info)
  • The most well-characterized protein kinases in the human genome are protein serine/threonine kinases and protein tyrosine kinases ( Methods Enzymol 200 (1991)">2 ). (cancerdiagnosisprognosis.org)
  • Another kinase class in which the amino acid serine is central in phosphoryl-group transfer is the serine kinases. (pharmacology2000.com)
  • Akt, a key target of the PI3 kinase, is a serine/threonine kinase that plays critical roles in the modulation of cell development, growth and survival [ 8 - 10 ]. (biomedcentral.com)
  • The serine/threonine protein kinase Akt plays an essential role in regulating various critical cellular functions, such as cell growth, proliferation, survival and metabolism [ 1 ]. (biomedcentral.com)
  • A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. (lookformedical.com)
  • The AXL protein is characterized by an extracellular structure consisting of two fibronectin type 3-like repeats and two immunoglobulin-like repeats along with its intracellular tyrosine kinase domain. (wikipedia.org)
  • The dimerization domain spans approximately 70 amino acid residues and contains a central phenylalanine zipper motif, which is formed by stacking of the aromatic side chains from 10 phenylalanine residues. (wikipedia.org)
  • Analysis of mutants of the SRC kinase family member HCK supports this model and shows the role of two residues, Y390 and K7, on its degradation following activation. (bvsalud.org)
  • The structure consists of two distinct alpha helical structural domains: the N-terminal domain which seems to have a purely structural role and the C-terminal domain which is sufficient for catalytic activity and contains all residues that interact with Ras. (embl.de)
  • The phosphorylated tyrosine residues together with their immediate flanking sequences function as binding sites for signaling molecules containing src homology 2 (SH2) domains. (yale.edu)
  • It encodes a 68 kDa nonreceptor type PTP containing 2 tandem Src homology (SH2) domains, a catalytic domain, and a COOH-terminal tail of 100 amino acid residues 15 . (cancerbiomed.org)
  • This resistance was via activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) axis. (cancerdiagnosisprognosis.org)
  • In general, Janus family tyrosine kinases (JAKs) bind to the intracellular components of cytokine receptors, and are, in turn, bound by STATs upon cytokine signaling. (medscape.com)
  • The tyrosine kinase involved in the system is described as a Janus kinase (JAK). (pharmacology2000.com)
  • Highlighted is the pathway mediated by cytokines via the cytokine receptor and JAK (Janus kinase, a tyrosine kinase). (pharmacology2000.com)
  • These receptors elicit a signaling cascade that enhances phagocytic activity and activates the production of pro-inflammatory cytokines, chemokines, reactive oxygen and nitrogen species, and antimicrobial peptides ( 3 ). (frontiersin.org)
  • Receptor tyrosine kinases undergo ligand dependent dimerization which activates their intrinsic protein tyrosine kinase (PTK) domains. (yale.edu)
  • Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. (nih.gov)
  • Another study indicated that LNK can suppress the interleukin-7/JAK/STAT signaling pathway to restrict pre B-cell progenitor expansion and leukemia development, which provided a pathogenic mechanism and a potential therapeutic approach for B-cell acute lymphoblastic leukemia with SH2B3 gene mutations. (wikipedia.org)
  • The first pathway involves direct activa- tion of RAB5-mediated endocytosis.12 The second pathway involves direct activation of ABL tyrosine kinase activity.13 Recent studies have indicated a potential role for altered RIN1 expression and function in tumor development and progression. (malt1inhibitor.com)
  • As it still remains unclear how these phosphorylations can influence the Ras pathway we have analyzed the ability of p60c-Src and Lck to phosphorylate these two Ras regulators and have compared the activity of the phosphorylated and unphosphorylated forms. (embl.de)
  • for example, protein kinase activation is part of the platelet activation signal pathway. (lookformedical.com)
  • SH2B adapter protein 3 (SH2B3), also known as lymphocyte adapter protein (LNK), is a protein that in humans is encoded by the SH2B3 gene on chromosome 12. (wikipedia.org)
  • In 2007, autosomal dominant mutations in signal transducer and activator of transcription-3 (STAT3) gene were identified as the molecular cause of this disease. (medscape.com)
  • In the last decade, new members of BCL2 gene family were discovered and cloned and were found to be differentially expressed in many types of cancer. (hindawi.com)
  • Among the different mechanisms, we can distinguish a direct effect on gene expression by regulation of transcription factors or an indirect effect through increases in mRNA stability. (shu.edu)
  • 5 In 1999 Indo et al cloned the full-length NTRK1 human gene encoding a 790-residue or 796-residue protein (TrkA receptor) with an intracellular domain containing a juxtamembrane region, a TK domain and a short C terminal tail. (eonco.info)
  • Tyrosine-protein kinase receptor UFO is an enzyme that in humans is encoded by the AXL gene . (wikipedia.org)
  • The protein encoded by this gene is a member of the receptor tyrosine kinase subfamily. (wikipedia.org)
  • The zebrafish embryo is an ideal model system for studying PGC migration due to 1) the transparency of the embryo, allowing in vivo analyses of cell migration and development, 2) the availability of various mutant stocks and the morpholino antisense oligo nucleotide gene knockdown system, and 3) the availability of PGC marker genes, for which localisation and functions are well characterised. (exeter.ac.uk)
  • Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. (cancerindex.org)
  • Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. (smw.ch)
  • Mature miRNA, along with Agonaute 2, forms an RNA-dependent silencing complex and binds to the 3′-UTRs of the target gene mRNAs with imperfect complementarity to cause their degradation or translational suppression [ 11 , 12 ]. (biomedcentral.com)
  • The proline rich homeodomain protein/haematopoietically expressed homeobox (PRH/HHEX), is a transcription factor encoded by the HHEX gene [ 1 - 3 ]. (biomedcentral.com)
  • The C-terminal domain is required for the transcriptional activation of the sodium-dependent bile acid co-transporter (NTCP) gene and is therefore likely to be required for the activation of transcription in other contexts [ 28 , 29 ]. (biomedcentral.com)
  • This gene encodes a member of the tripartite motif (TRIM) protein family. (nih.gov)
  • The human CD36 gene is located on chromosome 7 (7q11.2) and consists of 15 exons with a single peptide chain of 472 amino acids and has a predicted molecular mass of 53 kDa [ 3 ]. (e-dmj.org)
  • We found that total PDK1 is overexpressed in a large proportion of human en CB and found that a number of ports, the number of copies of the gene PDK1, increased PDPK1 Ht. (atpasepathway.com)
  • For example, mutations in the human kinome approach approximately 20%, some of which are drivers and many of which are passengers,[6] but the frequency of mutations in other gene families contributing to cancer remains to be established. (medscape.com)
  • Orally available small molecule compounds have recently been developed for the treatment of RA, and inhibitors of signalling cascades, specifically inhibitors of kinases, have reached advanced stages of clinical development. (medscape.com)
  • Finally, the molecular mechanism of FGF2 secretion is used in the lab to develop inhibitors of this process with great potential for the development of drugs for cancer therapy that block the function of FGF2 as a tumor cell survival factor. (db-engine.de)
  • We have also determined the crystal structure of the catalytic PTK domain of FGFR in complex with an ATP analogue or in complex with specific PTK inhibitors of FGFR activity and function. (yale.edu)
  • A major mechanism for the acquired resistance is the emergence of BTK cysteine 481 (C481) mutations, which disrupt the binding of covalent BTK inhibitors. (biomedcentral.com)
  • Additionally, adverse events due to the off-target inhibition of kinases other than BTK by covalent inhibitors are common. (biomedcentral.com)
  • BTK inhibitors, including covalent and non-covalent inhibitors, bind to the BTK kinase domain and block the catalytic activity of BTK, thereby suppressing subsequent Y223 autophosphorylation [ 6 ]. (biomedcentral.com)
  • 10. Direct binding of the proline-rich region of protein tyrosine phosphatase 1B to the Src homology 3 domain of p130(Cas). (nih.gov)
  • Requirements for Src kinase activity and FAK proline-rich motifs. (nih.gov)
  • The small adapter protein Grb2, for example, is bound through its SH3 domains to short, proline-rich sequences in the carboxy terminal tail of the guanine nucleotide-releasing factor Sos. (yale.edu)
  • The PRH monomer has three functional domains: a 136 amino acid N-terminal glycine-, alanine- and proline-rich domain, a central 60 amino acid proline-rich homeodomain, and a 73 amino acid acidic C-terminal domain (Fig. 1 ). (biomedcentral.com)
  • 3) Cytokine receptors represent another class. (pharmacology2000.com)
  • 2 All three Trk receptors are structured with an extracellular domain for ligand binding, a transmembrane region and an intracellular domain with a kinase domain. (eonco.info)
  • Neufeld G, Kessler O, Herzog Y. The interaction of Neuropilin-1 and Neuropilin-2 with tyrosine-kinase receptors for VEGF. (smw.ch)
  • However, the mechanisms whereby PSA-NCAM modulates glutamate receptors have not been studied. (auburn.edu)
  • This indicates that PSA, in addition to decreasing the desensitization of AMPA receptors may also act through another mechanism. (auburn.edu)
  • This work addresses the molecular basis of SKAP2-mediated SRC kinase regulation through the lens of their interaction capacities. (bvsalud.org)
  • This work opens new perspectives on the molecular mechanisms of SRC kinases activation, which could have significant therapeutic impact. (bvsalud.org)
  • This paper focusses on the current understanding of the cellular and molecular mechanisms driving sensitization induction resulting in IgE-mediated allergy. (biomedcentral.com)
  • In this review, we highlight the essential molecular mechanisms underlying the different phases of inflammation that are targeted by microRNAs to inhibit or accelerate restoration to tissue integrity and homeostasis. (frontiersin.org)
  • My recent research greatly focuses on the study of molecular mechanisms underlining cell movement. (exeter.ac.uk)
  • My research focuses on understanding the molecular mechanisms underlining cell migration, which are fundamental to a variety of physiological and pathological processes, including embryonic development, tissue repair, immune responses, and cancer cell metastasis. (exeter.ac.uk)
  • Interestingly, Nck1 and PTP1B in cells are found in a common molecular complex and their interaction is dependent on the SH3 domains of Nck1. (biomedcentral.com)
  • 2) Another receptor class involves ligand interaction with a membrane-integrated enzyme, for example receptor tyrosine kinases . (pharmacology2000.com)
  • The SH2 domain references 'Src-homology 2' which is described as a common structural feature among signaling molecules which promote protein-protein association through direct phosphotyrosine interaction. (pharmacology2000.com)
  • Single-stranded-DNA binding alters human replication protein A structure and facilitates interaction with DNA-dependent protein kinase. (nih.gov)
  • SH2 and SH3 domains are protein interaction domains. (lookformedical.com)
  • P61959.1 MADEKPKEGVKTENNDHINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQQQTGGVY 1367453_at NP_446195 8.92 hsp90 co-chaperone Cdc37 Cdc37 Rattus norvegicus " Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity. (nih.gov)
  • A main feature of the catalytic domain is the protrusion of a helical hairpin important for the nucleotide-exchange mechanism. (embl.de)
  • This entry represents the catalytic domain of the Ras guanine-nucleotide exchange factors. (embl.de)
  • In mammals, the Src homology (SH) domain-containing adaptor protein Nck (non-catalytic region of tyrosine kinase) includes two highly identical members, Nck1 and Nck2, which contain exclusively three SH3 domains at the N-terminus and one SH2 domain at the C-terminus [ 15 ]. (biomedcentral.com)
  • The encoded protein is an extensively palmitoylated membrane phosphoprotein containing a PDZ domain, a Src homology 3 (SH3) motif, and a guanylate kinase domain. (nih.gov)
  • Zeta chain of T-cell receptor associated protein kinase 70 (ZAP70) is a cytoplasmic tyrosine phosphoprotein. (cancerdiagnosisprognosis.org)
  • Binding of acetylcholine to an α-subunit binding domain induces a change in receptor geometry enabling increased ion flow down the central core 27 (see representation below). (pharmacology2000.com)
  • The overexpression of LNK led to the inhibition of anti-CD3 mediated NF-AT-Luc activation, indicating that LNK is involved in the mechanism of T cell-negative regulation. (wikipedia.org)
  • ZAP70 has a crucial role in T-cell receptor signaling activation and T-cell development ( Immunity 5(3) (1996)">18 ). (cancerdiagnosisprognosis.org)
  • 17. Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through interactions with and activation of c-Src. (nih.gov)
  • 19. Integrin-mediated activation of focal adhesion kinase is required for signaling to Jun NH2-terminal kinase and progression through the G1 phase of the cell cycle. (nih.gov)
  • 20. CrkII regulates focal adhesion kinase activation by making a complex with Crk-associated substrate, p130Cas. (nih.gov)
  • This leads to the activation of caspase 9, which then triggers a cascade of caspases activation (caspases 3 and 7) resulting in the morphological and biochemical changes associated with apoptosis. (hindawi.com)
  • Upon activation by the peptides, the dimeric receptor form is favored (association of two receptor monomers) and a previously associated tyrosine kinase transitions to the catalytically active form. (pharmacology2000.com)
  • As BCR (B-cell receptor) signaling requires protein tyrosine kinase (PTK) activation, CD19 recruits and amplifies the activation of Src-family protein tyrosine kinases such as Lyn and Fyn. (shu.edu)
  • Our current CAR constructs also include either a CD28 or 4-1BB costimulatory signaling domain to mimic a "second signal" that amplifies the activation of the CAR T cells, leading to a more robust signal to the T cell to multiply and kill the cancer cell. (shu.edu)
  • Binding of IGF-1 to its receptor causes receptor autophosphorylation and the activation of intrinsic tyrosine kinase. (biomedcentral.com)
  • These receptor tyrosine kinases (TK) are expressed in human neuronal tissue, and play an essential role in both the physiology of development and function of the nervous system through activation by neurotrophins (NTs). (eonco.info)
  • The tandem DH-PH domain of Sos (DH-PH-Sos) was defective in Rac activation but regained Rac stimulating activity when it was coexpressed with activated Ras. (embl.de)
  • Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. (embl.de)
  • Vascular endothelial growth factors (VEGFs) regulate blood and lymph vessel formation through activation of the type V receptor tyrosine kinases VEGFR-1, -2 and -3. (smw.ch)
  • Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. (lookformedical.com)
  • The epidermal growth factor receptor (EGFR) family, an essential component in PTKs activation, includes 4 members: human epidermal growth factor receptor (HER) 1 (also known as EGFR), HER2, HER3, and HER4. (cancerbiomed.org)
  • Background/Aim: Tyrosine kinases have crucial functions in cell signaling and proliferation. (cancerdiagnosisprognosis.org)
  • Receptor tyrosine kinases and cytoplasmic protein tyrosine kinases play a critical role in the control of many cellular processes including: cell proliferation, differentiation, metabolism, as well as cell survival and cell migration. (yale.edu)
  • MicroRNAs (miRNAs) are a class of small (~ 22 nucleotide long), non-coding RNAs in multicellular organisms, which modulate key cellular mechanisms of proliferation, metabolism and apoptosis via post-transcriptional regulation of hundreds of genes [ 10 ]. (biomedcentral.com)
  • Thus, in addition to its roles in survival and proliferation, IL-7R signaling shapes the Igh repertoire by activating underpinning mechanisms. (babraham.ac.uk)
  • In this setup, the ligand interacts with an extracellular domain, the consequence of which is a change in intracellular, cytoplasmic enzyme activity. (pharmacology2000.com)
  • In addition, various developmental disorders are caused by loss of function mutations in receptor tyrosine kinases. (yale.edu)
  • Src (sarcoma) is a group of proto-oncogenic tyrosine kinases. (pharmacology2000.com)
  • A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). (lookformedical.com)
  • Our subsequent studies of this phenomenon in the context of RSV (5), MMTV (6), and HIV (7) produced the first insights into the viral signals that influence frameshifting (a "slippery" heptanucleotide sequence and RNA secondary structure downstream) and attracted attention to a translational mechanism for generating diversity that has now been encountered in £.coli, yeast, and coronaviruses. (nih.gov)
  • However, we do not currently know the regulating mechanism and pathophysiological role of CD36 and its upstream and downstream targets on glucolipotoxicity in pancreatic β-cells. (e-dmj.org)
  • The aim of the current study is to elucidate the mechanism by which Nck1 depletion regulates hepatic insulin signaling. (biomedcentral.com)
  • A component of the Arp2-3 complex that is related in sequence and structure to ACTIN and that binds ATP. (lookformedical.com)
  • Arp2-3 complex binds WASP PROTEIN and existing ACTIN FILAMENTS, and it nucleates the formation of new branch point filaments. (lookformedical.com)
  • HN - 2017 MH - AC133 Antigen UI - D000071916 MN - D9.400.430.250 MN - D23.50.301.264.35.15 MN - D23.101.100.110.15 MS - A member of the prominin family, AC133 Antigen is a 5-transmembrane antigen occurring as several isoforms produced by alternative splicing which are processed into mature forms. (nih.gov)
  • Glucose uptake is regulated by several mechanisms, where insulin plays the most prominent role. (intechopen.com)
  • We will present regulatory mechanisms and modulators of insulin-mediated glucose uptake. (intechopen.com)
  • Role of Src family kinases and Rho family GTPases. (nih.gov)
  • Here we review recent experiments showing how VEGFR-2 is transported through intracellular vesicular compartments specified by Rab family GTPases, and discuss how different VEGF-A isoforms specify intracellular receptor trafficking. (smw.ch)
  • However, the long-term prognosis is still unsatisfactory due, primarily, to the high recurrence and invasion rates even after resec- tion (50%-70% at 5 years).4,5 Unfortunately, little is known about the cellular mechanisms underlying hepatocarcino- genesis. (malt1inhibitor.com)
  • 3] Each of these 6 acquired physiologic capabilities occurs during tumor development because of reactivation and changing of existing cellular programs utilized during embryogenesis and development. (medscape.com)
  • As illustrated below (Fig. 2), unconventional secretion of FGF2 occurs by direct translocation across plasma membranes, a process that involves sequential interactions of FGF2 with ATP1A1, Tec kinase and the phosphoinositide PI(4,5)P2 at the inner leaflet of the plasma membrane. (db-engine.de)
  • HN - 2017 (1997) MH - ADAM17 Protein UI - D000072198 MN - D8.811.277.656.675.374.102.375 MN - D9.400.430.500.375 MN - D12.776.395.33.375 MN - D23.50.301.264.35.57 MN - D23.101.100.110.57 MS - A disintegrin and metalloproteinase domain-containing protein that cleaves the membrane-bound precursor of TUMOR NECROSIS FACTOR-ALPHA to its mature form. (nih.gov)
  • Intramolecular FRET-based indicators have been engineered to monitor intracellular Ca 2+ , cyclic GMP, GTPase and kinase activities. (nature.com)
  • and (4) cytoplasmic signaling domain. (shu.edu)
  • E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription. (nih.gov)
  • The adaptor 3BP2/SH3BP2, an Abl Src homology domain 3 (SH3)-binding and Syk-kinases interacting protein, exhibits positive regulatory roles in T, natural killer (NK), and basophilic cells. (nih.gov)
  • In the sections that follow, I summarize our progress towards understanding the retroviral lifecycle (with emphasis upon viral entry, proviral integration, synthesis of reverse transcriptase by ribosomal frameshifting, and virus assembly) and some of the genes (especially src, Wnt-l/int-1, myc, and their relatives) implicated in retrovirus-induced neoplasia. (nih.gov)
  • This work has placed the Wnr-1 proto- oncogene and other members of the Wnt family among genes that affect differentiation and cell growth by cell-cell signalling and has focused attention upon the War receptor(s). (nih.gov)
  • Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes. (lookformedical.com)
  • We find that the Igh locus folds into semi-rigid subdomains and undergoes flexible looping of the V genes to its 3' end, reconciling two views of locus organization. (babraham.ac.uk)
  • We find skewing toward 3' V genes during de novo V-to-DJ recombination more severe than the fetal liver (FL) repertoire and uncover a role for IL-7R signaling in D-to-J recombination. (babraham.ac.uk)
  • Click on one of the cytokine subfamilies or receptor type to see the specific Jak and STAT molecules activated by members of the family. (rndsystems.com)
  • CAR T-cells have evolved from first generation constructs that contained an extracellular binding domain and intracellular signaling domain, to third generation structures that also include co-stimulatory molecules. (shu.edu)
  • These agents contain an Fv domain, which binds to tumor-selective antigens, and a bacterial toxin (Pseudomonas exotoxin), which can kill a cell when only one or a few molecules reach the target cell s cytoplasm. (nih.gov)
  • Proteolytic cleavage of the AXL extracellular domain by the metalloproteinases ADAM10 and ADAM17 can downregulate this signalling activity. (wikipedia.org)
  • The interactions between these two members of the Siglec family and the sialylated glycans present on HIV-1 envelope either induce or increase HIV-1 entry in conventional and unconventional target cells, thus contributing to viral dissemination and disease progression. (frontiersin.org)
  • For preserving β-cell function, it is essential to understand the cause and mechanisms about the progression of β-cells failure. (e-dmj.org)
  • Genetic and epigenetic mechanisms initiate the progression of cancer. (medscape.com)
  • This protein belongs to the Src homology 2-B (SH2B) adapter family. (wikipedia.org)
  • These advances have allowed a precise definition of substrates and intermediates in the reaction (3) and stimulated the development of in vitro assays (e.g., for att site binding (29) that use purified components. (nih.gov)
  • 18. Complexes of focal adhesion kinase (FAK) and Crk-associated substrate (p130(Cas)) are elevated in cytoskeleton-associated fractions following adhesion and Src transformation. (nih.gov)
  • 1973) Preparation and properties of Chromatin (III) nucleotide complexes for use in the study of enzyme mechanisms, Biochemistry 12:3714-3724. (nih.gov)
  • Functionally, the DIM domain is necessary and sufficient to bind to most activated and myristyl SRC kinases. (bvsalud.org)
  • In contrast, the three modules are necessary to bind SRC kinases at their steady state. (bvsalud.org)
  • These results suggest that inhibition of the PDK-1/PKB/Akt-mediated transduction step is the key mechanism for the inhibition of ISGU in adipocytes exposed to iAs III or MAs III , and possibly for impaired glucose tolerance associated with human exposures to iAs. (nih.gov)
  • and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. (lookformedical.com)