• The PDGFRB gene encodes a typical receptor tyrosine kinase, which belongs to the type III tyrosine kinase receptor (RTK) family and is structurally characterized by five extracellular immunoglobulin-like domains, a single membrane-spanning helix domain, an intracellular juxtamembrane domain, a split tyrosine kinase domain and a carboxylic tail. (wikipedia.org)
  • In the absence of ligand, PDGFRβ adopts an inactive conformation in which the activation loop folds over the catalytic site, the juxtamembrane region over a loop occluding the active site and the carboxy-terminal tail over the kinase domain. (wikipedia.org)
  • Alternatively, mutations in the kinase domain that stabilize a kinase active conformation result in constitutive activation. (wikipedia.org)
  • A fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome was conducted in a Drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. (sdbonline.org)
  • Thus, forced dimerization of the transmembrane and cytoplasmic domains of the GHR in the absence of the extracellular domain can lead to the constitutive activation of known GH signaling end points, supporting the view that proximity of Janus kinase 2 (JAK2) kinases is the essential element in signaling. (ku.dk)
  • Here we demonstrate that elevation of cyclic AMP (cAMP) levels in human umbilical vein endothelial cells (HUVECs) specifically attenuates ERK1,2 activation in response to either leptin or a soluble interleukin IL-6 receptor-α/IL-6 (sIL-6R-α/IL-6) trans-signalling complex but not protein kinase C activator phorbol 12-myristate 13-acetate. (gla.ac.uk)
  • The inhibitory effect of cAMP could not be reversed by inhibition of cAMP-dependent protein kinase (PKA) but was blocked by depletion of the alternative intracellular cAMP sensor exchange protein activated by cAMP 1 (Epac1), which is also required to observe SOCS-3 accumulation in response to cAMP. (gla.ac.uk)
  • Mammalian Cdc25 phosphatase is responsible for the dephosphorylation of Cdc2 and other cyclin-dependent kinases at Thr14 and Tyr15, thus activating the kinase and allowing cell cycle progression. (embl.de)
  • is a kinase enzyme , in particular a protein kinase , that phosphorylates the OH group of the amino-acid residues serine or threonine , which have similar side chains. (cloudfront.net)
  • In enzymology , the term serine/threonine protein kinase describes a class of enzymes in the family of transferases , that transfer phosphates to the oxygen atom of a serine or threonine side chain in proteins . (cloudfront.net)
  • Types include those acting directly as membrane-bound receptors ( Receptor protein serine/threonine kinase ) and intracellular kinases participating in Signal transduction . (cloudfront.net)
  • was in fact, the first Ser/Thr protein kinase to be discovered (in 1959 by Krebs et al. ). (cloudfront.net)
  • The gene codes for a protein kinase. (cloudfront.net)
  • Human homologs of the AKT8 oncogenic protein were identified in 1987.By 1995 it had been found that Akt kinases function as mitogen-activated kinases downstream from cell surface receptors that activate phosphoinositide 3-kinase . (cloudfront.net)
  • A family of proteins that inhibit signalling through tyrosine kinase receptors. (medecinesciences.org)
  • Both are linked to transformation due to deregulated kinase/phosphatase signaling or STAT5 gain-of-function (GOF) mutations. (nature.com)
  • [ 11 ] They revealed that whereas Noonan syndrome is caused by gain-of-function PTPN11 mutations, LEOPARD syndrome mutants are catalytically defective and act as dominant negative mutations that interfere with growth factor/Erk-mitogen-activated protein kinase-mediated signaling. (medscape.com)
  • The Src Homology 2 (SH2) domain is a major protein interaction module that is central to tyrosine kinase signaling. (eu.org)
  • Mitogen-Activated Protein Kinase Phosphatases" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (rush.edu)
  • This graph shows the total number of publications written about "Mitogen-Activated Protein Kinase Phosphatases" by people in this website by year, and whether "Mitogen-Activated Protein Kinase Phosphatases" was a major or minor topic of these publications. (rush.edu)
  • Below are the most recent publications written about "Mitogen-Activated Protein Kinase Phosphatases" by people in Profiles. (rush.edu)
  • Price TJ, Das V, Dussor G. Adenosine Monophosphate-activated Protein Kinase (AMPK) Activators For the Prevention, Treatment and Potential Reversal of Pathological Pain. (rush.edu)
  • Physiologically, the N-terminal domain of p126 binds the Src-homology 3 (SH3) domain of c-Abl, leading to activation of the MAPK/ERK2 kinase. (molcells.org)
  • Rabbit polyclonal to SYK.Syk is a cytoplasmic tyrosine kinase of the SYK family containing two SH2 domains.Plays a central role in the B cell receptor (BCR) response. (bioskinrevive.com)
  • Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. (nih.gov)
  • 1] J. Schlessinger and M. A. Lemmon, "SH2 and PTB domains in tyrosine kinase signaling. (chemdiv.com)
  • Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis. (bvsalud.org)
  • This mechanism is regulated by the activities of both protein-tyrosine kinases and protein tyrosine phosphatases. (drugbank.com)
  • The role of protein tyrosine kinases (PTKs) has been widely studied but less is known on the protein tyrosine phosphatases (PTPs) responsible for immunoregulation [ 3 ]. (biomedcentral.com)
  • At least 350 of the 500+ human protein kinases are serine/threonine kinases (STK). (cloudfront.net)
  • While the catalytic domain of these kinases is highly conserved , the sequence variation that is observed in the kinome (the subset of genes in the genome that encode kinases) provides for recognition of distinct substrates. (cloudfront.net)
  • is actually a family of protein kinases consisting of ~10 isozymes . (cloudfront.net)
  • Interferons (IFNs) induce early-response genes by stimulating Janus family (Jak) tyrosine kinases, leading to tyrosine phosphorylation of Stat transcription factors. (monocyte.eu)
  • Levels of cellular protein phosphorylation are modulated both by protein kinases and phosphatases. (rupress.org)
  • Although the importance of kinases in this process has long been recognized, an appreciation for the complex and fundamental role of phosphatases is more recent. (rupress.org)
  • Through extensive biochemical and genetic analysis, we now know that pathways are not simply switched on with kinases and off with phosphatases. (rupress.org)
  • Furthermore, kinases and phosphatases may work together to modulate the strength of a signal. (rupress.org)
  • Adding further complexity to this picture is the fact that both kinases and phosphatases can function in signaling networks where multiple kinases and phosphatases contribute to the outcome of a pathway. (rupress.org)
  • To fully understand this complex and essential regulatory process, the kinases and phosphatases mediating the changes in cellular phosphorylation must be identified and characterized. (rupress.org)
  • A variety of approaches, including biochemical purification, gene isolation by homology, and genetic screens, have been successfully used for the identification of putative protein kinases and phosphatases. (rupress.org)
  • Cytokine binding to the cell surface leads to phosphorylation of the receptor complex by receptor associated Janus kinases (JAKs) at tyrosine residues. (nature.com)
  • A subcategory of phosphohydrolases that are specific for MITOGEN-ACTIVATED PROTEIN KINASES. (rush.edu)
  • Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. (rush.edu)
  • AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP. (rush.edu)
  • SHP2 is a ubiquitously expressed protein tyrosine phosphatase required for growth factor signalling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. (astx.com)
  • A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. (umassmed.edu)
  • Our results suggest that a screening approach using protein crystallography is particularly useful to identify universal fragments for the conserved hydrophilic recognition sites found in target families such as SH2 domains, phosphatases, kinases, proteases, and esterases. (rcsb.org)
  • Regorafenib is an inhibitor of multiple protein kinases which exerts antitumor and antimetastatic activities in metastatic colorectal cancer (CRC). (oncotarget.com)
  • Intracellular signaling pathways that involve protein tyrosine kinases (PTKs) are critical for the control of most cellular processes. (chemdiv.com)
  • Both domains were initially identified as modules that recognize phosphorylated tyrosines in receptor tyrosine kinases and other signaling proteins. (chemdiv.com)
  • 2016) . A cross-species study of PI3K protein-protein interactions reveals the direct interaction of P85 and SHP2 . (sdbonline.org)
  • These data revealed an unexpected direct binding of Corkscrew, the Drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e , the human ortholog of the p110 catalytic subunit. (sdbonline.org)
  • The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (human GAB2 but not Drosophila Dos ). (sdbonline.org)
  • Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. (sdbonline.org)
  • This study identified that the protein most commonly affected in Noonan syndrome, the phosphatase SHP2, known in Drosophila as corkscrew (CSW) , controls life span, triglyceride levels, and metabolism without affecting ERK signaling pathway. (sdbonline.org)
  • Noonan syndrome (NS) and NS with multiple lentigines (NSML) cognitive dysfunction are linked to SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) gain-of-function (GoF) and loss-of-function (LoF), respectively. (sdbonline.org)
  • Oncogenic protein tyrosine phosphatases have long been viewed as drug targets of interest, and recently developed allosteric inhibitors of SH2 domain-containing phosphatase-2 (SHP2) have entered clinical trials. (figshare.com)
  • Measuring protein phosphorylation and expression in glioblastoma cells across 40 signaling pathway nodes in response to different drugs and for different oxygen tensions revealed that SHP2 antagonism has network-level, context-dependent signaling consequences that affect cell phenotypes (e.g., cell death) in unanticipated ways. (figshare.com)
  • Recombinant proteins including the catalytic domains of proteins tyrosine phosphatase 1B (PTP1B), T cell proteins tyrosine phosphatase (TCPTP), Src homology 848942-61-0 manufacture 2 (SH2) domain-containing tyrosine phosphatase 1 (SHP1), Src homology 2 (SH2) domain-containing tyrosine phosphatase 2 (SHP2), and hematopoietic proteins tyrosine phosphatase (HePTP) had been purified as previously referred to [15C18]. (gasyblog.com)
  • PTPN11 kodiert für die Nichtrezeptor Protein-Tyrosin-Phosphatase SHP2, die zwei Src-homology-2 (SH2) Domänen und eine Phosphatase-Domäne besitzt. (uni-goettingen.de)
  • Der zweite Teil der Arbeit konzentrierte sich auf die Bestimmung der Phosphatase-Aktivität von SHP2-Varianten in vitro mit Hilfe eines SOCS1-Luciferase-Assays. (uni-goettingen.de)
  • LEOPARD syndrome, also known as Noonan syndrome with multiple lentigines, is a rare autosomal dominant disorder most often caused by missense mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase SHP2. (medscape.com)
  • between the phosphatase domain and the C-SH2 domain of SHP2 which were improved using structure-guided design. (astx.com)
  • Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) is a nonreceptor phosphotyrosine phosphatase that promotes tumor progression in many types of cancer when activated by regulating the RAS signaling pathway. (scienceboard.net)
  • These compounds had a methyl group that occupies a pocket of the SHP2 autoinhibitory domain with partially hydrophobic characteristics. (scienceboard.net)
  • Upon PDGF binding the dimerization of receptor releases the inhibitory conformations due to auto-phosphorylation of regulatory tyrosine residues in trans fashion. (wikipedia.org)
  • Tyrosine residues 857 and 751 are major phosphorylation sites for the activation of PDGFRβ. (wikipedia.org)
  • The phosphorylation of proteins at tyrosine residues is critical in the growth signaling induced by Epo. (drugbank.com)
  • Those which bind phosphorylated tyrosine residues may recruit multi-phosphorylated substrates for the adjacent active domains and are more conserved, while the other class have accumulated several variable amino acid substitutions and have a complete loss of tyrosine binding capability. (embl.de)
  • The reversible phosphorylation of proteins on serine, threonine, and tyrosine residues represents a fundamental strategy used by eukaryotic organisms to regulate a host of biological functions, including DNA replication, cell cycle progression, energy metabolism, and cell growth and differentiation. (rupress.org)
  • OGT transfers O-GlcNAc moieties from UDP-GlcNAc to serine and threonine residues of proteins and O-GlcNAcase (OGA) catalyzes the opposite reaction to remove O-GlcNAc. (nature.com)
  • Different families of SH2 domains may have different binding specificity, which is usually determined by a few residues C-terminal with respect to the pY (positions +1 to +4). (eu.org)
  • The residue at pY+2 does not make direct side chain interactions with the SH2 domain, but aromatic residues are not allowed. (eu.org)
  • Positively charged residues are disfavoured at pY-1 and pY-2 due to the positively charged SH2 domain surface, but are tolerated when pY+1 and pY+3 are strong residues. (eu.org)
  • An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. (bvsalud.org)
  • Noonan syndrome and related disorders are caused by mutations in genes encoding for proteins of the RAS-ERK1/2 signaling pathway, which affect development by enhanced ERK1/2 activity. (sdbonline.org)
  • Involvement of SH2-containing phosphotyrosine phosphatase Syp in erythropoietin receptor signal transduction pathways. (drugbank.com)
  • The discovery of phosphotyrosine phosphatases that contain SH2 domains suggests roles for these molecules in growth factor signaling pathways. (drugbank.com)
  • We found that Syp, a phosphotyrosine phosphatase, widely expressed in all tissues in mammals became phosphorylated on tyrosine after stimulation with Epo in M07ER cells engineered to express high levels of human EpoR. (drugbank.com)
  • To be active SHP-2 needs a disruption between N-SH2 and tyrosine phosphatase domain which is induced by its binding of the phosphotyrosine-containing motifs with its signalling partners. (uni-goettingen.de)
  • SH2 domains are phosphotyrosine recognition domains, often mediating transient interactions with target proteins. (eu.org)
  • SH2 (Src homology region 2) and PTB (phosphotyrosine-binding) domains are small protein modules that mediate protein-protein interactions involved in many signal transduction pathways. (chemdiv.com)
  • Approximately 40-50% of NS cases are due to missense mutations in the PTPN11 gene which encodes SHP-2, a non-receptor protein tyrosine phosphatase. (uni-goettingen.de)
  • Alle bisher gefundenen Mutationen in PTPN11 verhindern die Bindung zwischen N-SH2 und PTP, was zu einer Überaktivität der Phosphatase führt.Im Rahmen der vorliegenden Arbeit sollten drei Aspekte untersucht werden. (uni-goettingen.de)
  • [ 4 ] Molecular studies have proven that LEOPARD syndrome and Noonan syndrome are allelic disorders caused by different missense mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located at band 12q24.1. (medscape.com)
  • [ 9 ] Because the vast majority of mutations reside in and around the broad intramolecular interaction surface between the N-SH2 and PTP domains of the PTPN11 protein, they have been suggested to affect the intramolecular N-SH2/PTP binding in the absence of a phosphopeptide, leading to excessive phosphatase activities. (medscape.com)
  • Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. (nih.gov)
  • The catalytic domain of this dual-specificity phosphatase has recently been mapped to the 180 most C-terminal amino acids. (embl.de)
  • The term RASopathies includes disorders with mutations in the genes that code for the proteins of the RAS/MAPK pathway, such as neurofibromatosis type 1, Noonan syndrome, Legius syndrome, LEOPARD syndrome, Costello syndrome, and cardiofaciocutaneous syndrome. (medscape.com)
  • Repetto MV, Winters MJ, Bush A, Reiter W, Hollenstein DM, Ammerer G, Pryciak PM, Colman-Lerner A. CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5. (umassmed.edu)
  • The human NCK1 (Nckα) and NCK2 (Nckβ/GRB4) SH2 domains show a degree of partner specificity but share the same mode of ligand binding ( Frese,2006 ) and belong to the class IA family which contains an aromatic residue (Phe) at the specificity-determining βD5 position ( Kaneko,2010 ). (eu.org)
  • Three loops surround the peptide binding pocket and are important for specificity: Because these loops can be flexible, considerable variation in peptide binding can apply for any given SH2 domain. (eu.org)
  • F-box protein specificity for g1 cyclins is dictated by subcellular localization. (umassmed.edu)
  • Adaptor Proteins, Signal Transducing" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (childrensmercy.org)
  • Below are the most recent publications written about "Adaptor Proteins, Signal Transducing" by people in Profiles. (childrensmercy.org)
  • STP, serine/threonine protein phosphatase. (rupress.org)
  • Two of the five PDGF isoforms activate PDGFRβ (PDGF-B and PDGF-D). The activated receptor phosphorylates itself and other proteins, and thereby engages intracellular signaling pathways that trigger cellular responses such as migration and proliferation. (wikipedia.org)
  • They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. (childrensmercy.org)
  • Siglec-E, a mouse orthologue of human Siglec-9, is a sialic acid binding lectin predominantly expressed on the surface of myeloid cells to transduce inhibitory signal via recruitment of SH2-domain containing protein tyrosine phosphatase SHP-1/2 upon binding to its sialoglycan ligands. (biomedcentral.com)
  • SHIP function is thought to require the dual engagement of the BCR and negative regulatory coreceptors as only the latter appear capable of recruiting SHIP from the cytosol to the plasma membrane by the virtue of phosphorylated immunoreceptor tyrosine-based inhibitory motifs. (crick.ac.uk)
  • Our data reveal auto-inhibitory SHIP activation by the activated BCR and suggest an unexpected negative-regulatory capacity of immunoreceptor tyrosine-based activation motifs in Igα and Igβ. (crick.ac.uk)
  • Thus, the two substrates of this enzyme are ATP and a protein , whereas its two products are ADP and phosphoprotein . (cloudfront.net)
  • PTPase domains consist of about 300 amino acids. (embl.de)
  • Tyrosine phosphorylation of shc in response to B cell antigen receptor engagement depends on the SHIP inositol phosphatase. (musc.edu)
  • The SH2 domain-containing inositol 5'-phosphatase (SHIP) plays a key role in preventing autoimmune phenomena by limiting antigen-mediated B cell activation. (crick.ac.uk)
  • Another negative regulator of hematopoietic cell development and function is SHP-1 (SRC homology 2 (SH2)-containing tyrosine phosphatase 1), that is mainly expressed in hematopoietic and lymphoid cells [ 8 ]. (biomedcentral.com)
  • Mutations identified in many SH2 domain-containing proteins as well as the SH2 domain itself are associated with human diseases ranging from cancers, diabetes, to immunodeficiencies. (eu.org)
  • EC 3.1.3.48 ) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. (embl.de)
  • They are able to bind specific motifs containing a phosphorylated tyrosine residue, propagating the signal downstream by promoting protein-protein interactions and/or modifying enzymatic activities. (eu.org)
  • For instance, forcing PDGFRβ into close proximity of each other by overexpression or with antibodies directed against the extracellular domain. (wikipedia.org)
  • Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers of the growth hormone receptor (GHR) signaling domain. (ku.dk)
  • The entire extracellular domain of the GHR was replaced by the hemagglutinin-tagged zipper sequence of either the c-Fos or c-Jun transcription factor (termed Fos-GHR and Jun-GHR, respectively). (ku.dk)
  • These foam cells in turn produce more inflammatory cytokines and growth factors to promote the migration of the quiescent vascular smooth muscle cells (VSMCs) in the medial layer to intima and activate VSMC proliferation and increased synthesis of extracellular matrix proteins, resulting in the thickening of intima and occlusion of the blood vessel [ 2 , 3 , 4 ]. (biomedcentral.com)
  • Structurally, all known receptor PTPases, are made up of a variable length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain. (embl.de)
  • Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains or carbonic anhydrase-like domains in their extracellular region. (embl.de)
  • The functions of SH2 and PTB domains include targeting of their host proteins to different cellular compartments, assembly of key components of signaling pathways in response to extracellular signals, and the control of autoinhibition, activation and dimerization of their host proteins. (chemdiv.com)
  • Furthermore, Syp appeared to bind directly to tyrosine-phosphorylated EpoR in M07ER cells. (drugbank.com)
  • Both NH2-terminal and COOH-terminal SH2 domains of Syp, made as glutathione S-transferase fusion proteins, were able to bind to the tyrosine-phosphorylated EpoR in vitro. (drugbank.com)
  • CagA can specifically bind to the SH2 domain of Src homology 2 (SH2)-containing protein tyrosine phosphatase (SHP-2), which induces spatial configuration change of SHP-2 and activates it [ 40 ]. (biomedcentral.com)
  • Subsequent studies have shown that, while binding of SH2 domains to their target proteins is strictly regulated by tyrosine phosphorylation, most PTB domains actually bind to their (nonphosphorylated) targets constitutively. (chemdiv.com)
  • O-GlcNAcylation regulates the transcriptional activity of p53, c-Myc, FoxO1 and CREB, as well as components of the basal transcription machinery, for example, the C-terminal domain of RNA polymerase II. (nature.com)
  • Genetic interaction of mammalian IFT-A paralogs regulates cilia disassembly, ciliary entry of membrane protein, Hedgehog signaling, and embryogenesis. (childrensmercy.org)
  • Importantly, regorafenib augmented SHP-1 activity by direct disruption of the association between N-SH2 and catalytic PTP domain of SHP-1. (oncotarget.com)
  • The cytotoxin-associated gene A ( cagA ) is one of the most important virulence genes of H. pylori , which is located at the end of cag pathogenicity island ( cag PAI) and encodes the 120-145 kDa CagA protein [ 7 ]. (biomedcentral.com)
  • SHP-2 can hamper the TRIF (TIR-domain-containing adapter-inducing interferon-β) adaptor protein-dependent TLR4 and TLR3 signal transduction with a consequent block of the pro-inflammatory cytokine production [ 7 ]. (biomedcentral.com)
  • Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. (nature.com)
  • A model of Cdc25 phosphatase catalytic domain and Cdk-interaction surface based on the presence of a rhodanese homology domain. (embl.de)
  • Most NS causative defects are located in or close to the N-SH2 and protein tyrosine phosphatase interacting surfaces which are thought to alter N-SH2/PTP interactions and destabilize the inactive conformation without altering the SHP-2 catalytic domain. (uni-goettingen.de)
  • Wen Y, Yang S, Wakabayashi K, Svensson MND, Stanford SM, Santelli E, Bottini N. RPTPα phosphatase activity is allosterically regulated by the membrane-distal catalytic domain. (ucsd.edu)
  • In the absence of coreceptor ligation, SHIP translocates to sites of BCR activation through a concerted action of the protein adaptor unit Dok-3/Grb2 and phosphorylated BCR signaling components. (crick.ac.uk)
  • Deletion of the N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 blocked the effect of regorafenib-induced SHP-1 activity, growth inhibition and a decrease of p-STAT3 Tyr705 expression, suggesting that regorafenib triggers a conformational change in SHP-1 by relieving its autoinhibition. (oncotarget.com)
  • The most promising fragments were successfully used to replace the phospho-tyrosine and resulted in novel nonpeptidic high affinity inhibitors. (rcsb.org)
  • Src Homology 2 (SH2) domains are small modular domains found within a great number of proteins involved in different signalling pathways. (eu.org)
  • This entry represents the PTPase domain found in several tyrosine-specific protein phosphatases (PTPases). (embl.de)
  • The cytoplasmic region generally contains two copies of the PTPase domain. (embl.de)
  • Previous studies implicated protein-tyrosine phosphatase (PTP) activity in the control of IFN-regulated Jak/Stat signaling, but the specific PTPs responsible remained unidentified. (monocyte.eu)
  • Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. (embl.de)
  • Several different binding motifs are known, for example: pYEEI (Src-family SH2 domains), pY [IV]. (eu.org)
  • The C-terminal half of the SH2 domain exhibits greater structural variability and provides a platform for accommodating different kinds of SH2-binding motifs. (eu.org)
  • Intrinsic brain RAS is an enzyme-neuropeptide system having functional components (angiotensinogen, peptidases, angiotensin, and specific receptor proteins) with important biological and neurobiological activities in the brain. (hindawi.com)
  • The systematic name of this enzyme class is ATP:protein phosphotransferase (non-specific) . (cloudfront.net)
  • These were formerly included in EC number '2.7.1.37', which was a general EC number for any enzyme that phosphorylates proteins while converting ATP to ADP (i.e. (cloudfront.net)
  • Protein phosphorylation can regulate enzyme function, mediate protein-protein interactions, alter subcellular localization, and control protein stability. (rupress.org)
  • In NCK SH2 domains, the EF loop is positioned away from the BG loop, exposing the pY+3 binding pocket where the side chain of Val forms tight interactions. (eu.org)
  • Functional diversity between PTPases is endowed by regulatory domains and subunits. (embl.de)
  • The protein encoded by this gene is a member of the signal-regulatory-protein (SIRP) family, and also belongs to the immunoglobulin superfamily. (nih.gov)
  • Lymphocyte activation gene-3 (LAG-3) is a coinhibitory receptor associated with impaired T-cell function and is frequently coexpressed with programmed cell death protein-1 (PD-1) in the context of human cancers. (aacrjournals.org)
  • SRC homology 2 (SH2)-containing tyrosine phosphatase-2 (SHP-2) has a controversial effect on lymphocyte signaling. (biomedcentral.com)
  • lymphocyte cytosolic protein 2 (SH2 domain. (wikigenes.org)
  • The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. (nature.com)
  • The Gab1 protein is a docking site for multiple proteins involved in signaling by the B cell antigen receptor. (musc.edu)
  • Die N-terminale SH2-Domäne (N-SH2) ist ein konformativer Schalter: entweder interagiert N-SH2 mit der Phosphatase-Domäne (PTP) und hemmt diese, oder sie bindet an ein Phosphotyrosin-Motiv von Signalpartnern (z.B. Gab1) und lässt die Phosphatase-Domäne frei und aktiv. (uni-goettingen.de)
  • By performing proximity labeling and proteomic analysis, we identified scavenger receptor CD36 as a cell surface protein interacting with Siglec-E. Further experiments performed in HEK293T cells transiently overexpressing Siglec-E and CD36 and peritoneal macrophages demonstrated that depletion of cell surface sialic acids by treatment with sialyltransferase inhibitor or sialidase did not affect interaction between Siglec-E and CD36 but retarded Siglec-E-mediated inhibition on oxidized LDL uptake. (biomedcentral.com)
  • However, the ability of phosphatases to regulate many targets directly or indirectly and to both promote and antagonize oncogenic signaling may make the efficacy of phosphatase inhibition challenging to predict. (figshare.com)
  • Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the PDGFRB gene. (wikipedia.org)
  • Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
  • The binding affinity of an SH2 domain to a pTyr containing ligand is moderate, with the typical affinity range between 0.1 µМ to 10 µМ for equilibrium dissociation constant values (Kd) ( Kaneko,2012 ). (eu.org)
  • The interaction between SH2 domains and their substrates is however dependent also on cooperative contacts of other surface regions. (eu.org)
  • Cloning of two members of the SIRP alpha family of protein tyrosine phosphatase binding proteins in cattle that are expressed on monocytes and a subpopulation of dendritic cells and which mediate binding to CD4 T cells. (medecinesciences.org)
  • The Tir protein of EPEC binds NCK1/NCK2 SH2 domains through a high affinity pYDEV motif ( Frese,2006 ). (eu.org)
  • Another PTP involved in the immune processes is PTPMEG, a cytosolic phosphatase expressed in the thymus that is able to dephosphorylates TCRζ ITAMs in vitro . (biomedcentral.com)