• The phosphorylation mediates activation of tyrosine kinase SHP2. (wikipedia.org)
  • Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. (nature.com)
  • We found that O-GlcNAcylation and tyrosine phosphorylation act together to trigger pYSTAT5 levels and oncogenic transcription in neoplastic cells. (nature.com)
  • 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)
  • Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. (nature.com)
  • Cytokine binding to the cell surface leads to phosphorylation of the receptor complex by receptor associated Janus kinases (JAKs) at tyrosine residues. (nature.com)
  • 7 The JAKs also trigger the activation and tyrosine phosphorylation of STAT5, causing parallel dimerization, nuclear translocation and tetramerization of STAT5. (nature.com)
  • Binding of Sema4D to plexin-B1 stimulates the intrinsic tyrosine kinase activity of ErbB-2, resulting in the phosphorylation of both plexin-B1 and ErbB-2. (rupress.org)
  • Our data indicate that ErbB-2 is an important component of the plexin-B receptor system and that ErbB-2-mediated phosphorylation of plexin-B1 is critically involved in Sema4D-induced RhoA activation, which underlies cellular phenomena downstream of plexin-B1, including axonal growth cone collapse. (rupress.org)
  • This is consistent with reports that the slow phosphorylation of tyrosine residues of the Lat adaptor associates with recruitment and activation of the phospholipase Plcγ1, thereby constituting an important kinetic bottleneck for ligand discrimination 11 . (nature.com)
  • While the phosphorylation of tyrosine residues in the immunoreceptor tyrosine-based activation motifs (ITAMs) of Cd3 and the inducible interaction between Cd3 and Zap70 remained largely unaffected, the abundance of activated Zap70 dropped with decreasing peptide affinity. (nature.com)
  • Phosphorylation at Tyr 1068 allows binding of the SH2 domain of the cytosolic adaptor Grb2. (rndsystems.com)
  • The activity of tyrosine hydroxylase is regulated by phosphorylation and through the regulation of its expression. (xray.cz)
  • All phosphorylation sites (Ser-8, Ser-19, Ser-31 and Ser‑40) are located within the regulatory domain [2]. (xray.cz)
  • Phosphorylation at Ser-40 by cyclic AMP-dependent protein kinase (PKA) induces the most potent activation of tyrosine hydroxylase. (xray.cz)
  • It has been proposed that phosphorylation of Ser-40 alters the conformation of the regulatory domain and its interaction with the catalytic domain. (xray.cz)
  • Phosphorylation at Ser‑19 induces binding of the 14‑3‑3 protein, which affects the structure of the regulatory domain and protects it against dephosphorylation (at phosphorylated Ser-40) and its degradation [4, 5]. (xray.cz)
  • A unique pathogenic fibroblast growth factor receptor gain-of-function mutation promotes formation of the complex responsible for phosphorylation of A-loop tyrosines by eliminating this repulsive force. (nyu.edu)
  • Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) activated the FL receptor, as determined by tyrosine phosphorylation. (jneurosci.org)
  • In order to become active, the CR3 kinase domain must be converted to its active form by phosphorylation of the activation loop. (news-medical.net)
  • The protein tyrosine kinase (PTK) Lck phosphorylates the ζ-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. (harvard.edu)
  • The binding of extracellular matrix ligands to integrins triggers autophosphorylation at Tyr-397, and activation of FAK through phosphorylation of Tyr residues (Tyr-576 and Tyr577) in the kinase domain activation loop. (fishersci.com)
  • For example, cell adhesion to a fibronectin substratum involves concurrent activation of Src and phosphorylation of the FAK activation loop. (fishersci.com)
  • In addition, phosphorylation of other Tyr residues (Tyr-925, and Tyr-861) creates binding sites for SH2 domains of intracellular signaling molecules such as Src, PI3 kinase, and Grb2. (fishersci.com)
  • Activation of JAK-1 and TYK-2 leads to phosphorylation of STAT1 and STAT2. (cdc.gov)
  • The intact receptor lacks tyrosine kinase activity, but binding of GH and dimerization results in association with JAK2, a member of the Janus kinase family, which results in self-phosphorylation of the JAK2 and a cascade of phosphorylation of cellular proteins. (medscape.com)
  • Cytoplasmic region contains a number of tyrosine residues, which likely act as ITIMs. (wikipedia.org)
  • Ligand binding induces receptor dimerization and autophosphorylation on multiple tyrosine residues. (rndsystems.com)
  • Inhibition of the kinase domain is halted through binding of the Ras-binding domain, or residues 155-227 of the protein, to the Ras-GTP effector domain. (news-medical.net)
  • In addition to autoinhibition, CR3 is also inhibited when the protein is not post-translationally phosphorylated at certain serine and tyrosine residues in the CR2 hinge region. (news-medical.net)
  • 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)
  • The 3D crystal structure of the Smaug RNA-binding region shows a cluster of positively charged residues on the Smaug-SAM domain, which could be the RNA-binding surface. (embl.de)
  • Residues that compose the RNA-binding surface are conserved in a subgroup of SAM domain-containing proteins, suggesting that the function of the domain is conserved from yeast to humans. (embl.de)
  • NEPH1 triggers AP-1 activation similarly to nephrin but requires the presence of Tec family kinases for efficient transactivation. (nih.gov)
  • Epidermal growth factor receptor (EGF R, also known as ErbB1 and HER1) is the founding member of the ErbB family of receptor tyrosine kinases. (rndsystems.com)
  • The trk receptors, a family of receptor tyrosine kinases including trkA, trkB, and trkC, serve as the principal signal-transducing receptors for the neurotrophins ( Barbacid, 1994 ). (jneurosci.org)
  • Upon activation, STAT5 is phosphorylated by receptor tyrosine kinases and, in turn, forms homodimers or hererodimers with other family members through its SH2 domains. (biolegend.com)
  • First identified during PCR-based cloning of a human neuroblastoma cell line in search of tyrosine kinases similar to tropomyosin-receptor-kinase (Trk) neurotropic receptors, ROR1, along with the related receptor tyrosine kinase (RTK) ROR2, was catalogued as an "orphan" receptor due to the fact its related ligand remained elusive. (peprotech.com)
  • In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. (embl.de)
  • In contrast to the case of many kinases, we have found that the activation loop of FLT3 is not essential for its activation. (lu.se)
  • The extracellular domain of SIRP α binds to CD47 and transmits intracellular signals through its cytoplasmic domain. (wikipedia.org)
  • The canonical form of this glycosylated transmembrane protein has an N-terminal extracellular region with five immunoglobulin-like domains, a transmembrane region, and an intracellular tyrosine kinase domain at the C-terminus. (nih.gov)
  • Upon activation by its cytokine ligand, stem cell factor (SCF), this protein phosphorylates multiple intracellular proteins that play a role in in the proliferation, differentiation, migration and apoptosis of many cell types and thereby plays an important role in hematopoiesis, stem cell maintenance, gametogenesis, melanogenesis, and in mast cell development, migration and function. (nih.gov)
  • Alternative splicing affects both the extracellular ligand-binding domains and the intracellular signal-transducing domains of the trks ( Barbacid, 1994 ). (jneurosci.org)
  • its intracellular (COOH-terminal) region contains two PTP catalytic domains, and the extracellular region is highly variable due to alternative splicing of exons (designated A, B, and C, respectively) as well as differing levels of glycosylation. (bdbiosciences.com)
  • ROR1 is expressed as a glycoprotein containing extracellular immunoglobulin (Ig)-like, Frizzled, and Kringle domains, as well as an intracellular region containing a tyrosine kinase domain. (peprotech.com)
  • The most critical of these proteins is the signal transducer and activator of transcription 5b (STAT5b), which couples GH binding to the activation of gene expression that leads to the intracellular effects of GH, including synthesis of IGF-I, insulin-like growth factor binding protein 3 (IGFBP3), and ALS. (medscape.com)
  • In contrast, Btk signaling sustains growth of several B-cell neoplasms which may be treated with tyrosine kinase inhibitors (TKIs). (rcsb.org)
  • The treatment paradigm of AML patients harboring FLT3 mutations (30%) has been modified by the discovery of tyrosine kinase inhibitors. (dovepress.com)
  • The discovery of ALK gene rearrangements and the development of tyrosine kinase inhibitors (TKIs) that target them have achieved unprecedented success in the management of patients with ALK-positive NSCLC. (medpagetoday.com)
  • Using a panel of kinase inhibitors, we found ALK inhibitor AZD3463 selectively inhibited the activation and downstream signaling of FLT3-ITD and did not affect the wild-type FLT3 (FLT3-WT). (lu.se)
  • Effective assessment of low times MET amplification in pleural effusion after epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) acquired resistance: Cases report. (cdc.gov)
  • mutation of a centrally located tyrosine residue dramatically lowers the affinity of NEPH1 for podocin. (nih.gov)
  • SIRP α polymorphisms are found in ligand-binding IgSF V-set domain but it does not affect ligand binding. (wikipedia.org)
  • The kinetic proofreading model postulates that TCR ligand discrimination is due to several signaling steps that introduce a delay between ligand binding and T cell activation. (nature.com)
  • This implies that the pMHC ligand dwell time on the TCR determines the probability of completing a series of signaling events leading to T cell activation 5 . (nature.com)
  • In particular, it is unclear whether ligand affinity uniformly affects the different signaling pathways involved in T cell activation. (nature.com)
  • Under physiological conditions, the energetic gain resulting from ligand-induced dimerization of extracellular domains overcomes this opposing clash, stabilizing the A-loop-transphosphorylating dimer. (nyu.edu)
  • a deletion in close proximity to this domain is likely to affect ligand specificity. (jneurosci.org)
  • We report a 2.5 A crystal structure of the functional core of SCF bound to the extracellular ligand-binding domains of KIT. (rcsb.org)
  • 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)
  • 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)
  • Wnt-5a has since been suggested as a candidate ligand for ROR1, and ROR1 has been implicated to function as a pseudokinase, promoting proliferation and resistance to apoptosis in cancer cells through interaction with Wnt-5a, and TCL1-co-activation of AKT. (peprotech.com)
  • Although NT-3, NT-4, and BDNF activate FL receptors, only BDNF is capable of robust but decreased activation of ED receptors. (jneurosci.org)
  • What are physical characteristics found in all tyrosine kinase receptors? (flashcardmachine.com)
  • Receptors for the Fc region of IgG (Fc gamma Rs) are members of the Ig superfamily that function in the activation or inhibition of immune responses such as degranulation, phagocytosis, ADCC (antibody-dependent cellular toxicity), cytokine release, and B cell proliferation (1‑3). (novusbio.com)
  • Here, we uncovered the structural mechanism by which certain XLA mutations in the SH2 domain strongly perturb Btk activation. (rcsb.org)
  • Using a combination of molecular dynamics (MD) simulations and small-angle X-ray scattering (SAXS), we discovered an allosteric interface between the SH2 and kinase domain required for Btk activation and to which multiple XLA mutations map. (rcsb.org)
  • 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)
  • Most CFH gene mutations associated with atypical hemolytic-uremic syndrome affect a region of the complement factor H protein known as the C-terminal domain. (medlineplus.gov)
  • Clinical characteristics, tumor, node, metastasis status, and mutation rate in domain of epidermal growth factor receptor gene in serbian patients with lung adenocarcinoma. (cdc.gov)
  • 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)
  • Mature mouse IFN‑ alpha / beta R1 consists of a 403 aa extracellular domain (ECD), a 20 aa transmembrane segment, and a 141 aa cytoplasmic domain (4). (rndsystems.com)
  • IFN‑ alpha / beta R1 activation depends on tyrosine phoshorylation as well as palmitoylation of its cytoplasmic domain (8, 9). (rndsystems.com)
  • The transmembrane beta subunit contains tyrosine kinase activity on its cytoplasmic domain that results in rapid receptor autophosphorylation. (weeksmd.com)
  • Fc gamma Rs that deliver an activating signal either have an intrinsic immunoreceptor tyrosine-based activation motif (ITAM) within their cytoplasmic domains or associate with one of the ITAM-bearing adapter subunits, FcR gamma or zeta (3, 5). (novusbio.com)
  • Sotyktu (deucravacitinib) is a tyrosine kinase 2 (TYK2) inhibitor. (centerwatch.com)
  • Usefulness of Bronchoscopic Rebiopsy of Non-Small Cell Lung Cancer with Acquired Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor. (cdc.gov)
  • Activation of the kinase towards exogenous substrates is apparently preceeded by this insulin-dependent autophosphorylation reaction of the beta subunit. (weeksmd.com)
  • We report now that NEPH1 belongs to a family of three closely related proteins that interact with the C-terminal domain of podocin. (nih.gov)
  • Src Homology 2 (SH2) domains are small modular domains found within a great number of proteins involved in different signalling pathways. (eu.org)
  • SH2 domains are phosphotyrosine recognition domains, often mediating transient interactions with target proteins. (eu.org)
  • FAK's ability to bind numerous structural and signaling proteins via a variety of interactions is important for FAK activation level, and for FAK interaction with a variety of substrates localized to sites of cell adhesion. (fishersci.com)
  • Widespread domain in signalling and nuclear proteins. (embl.de)
  • The sterile alpha motif (SAM) domain is a putative protein interaction module present in a wide variety of proteins [ ( PUBMED:9007998 ) ] involved in many biological processes. (embl.de)
  • There are 64647 SAM domains in 49933 proteins in SMART's nrdb database. (embl.de)
  • Taxonomic distribution of proteins containing SAM domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with SAM domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing SAM domain in the selected taxonomic class. (embl.de)
  • All three T cell activation motifs in ζ bind ZAP70 tandem-SH2 domains in vitro , forming a 1:3 complex. (harvard.edu)
  • 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)
  • Fc receptor-dependent antibody functions are also involved in activation of downstream adaptive immune responses by facilitating antigen presentation or by stimulating the secretion of inflammatory mediators ( 12 , 13 ). (frontiersin.org)
  • This results in allosteric inhibition of receptor-mediated activation of TYK2 and its downstream activation of Signal Transducers and Activators of Transcription (STATs) as shown in cell-based assays. (centerwatch.com)
  • Stem cell factor (SCF) binds to and activates the KIT receptor, a class III receptor tyrosine kinase (RTK), to stimulate diverse processes including melanogenesis, gametogenesis and hematopoeisis. (rcsb.org)
  • Sotyktu binds to the regulatory domain of TYK2, stabilizing an inhibitory interaction between the regulatory and the catalytic domains of the enzyme. (centerwatch.com)
  • The Tir protein of EPEC binds NCK1/NCK2 SH2 domains through a high affinity pYDEV motif ( Frese,2006 ). (eu.org)
  • We show here that the SAM domain of Saccharomyces cerevisiae Vts1 binds RNA with the same specificity as Smaug and that Vts1 induces transcript degradation through a mechanism involving the cytoplasmic deadenylase CCR4. (embl.de)
  • The structure reveals a 'wrapping' SCF-recognition mode by KIT, in which KIT adopts a bent conformation to facilitate each of its first three immunoglobulin (Ig)-like domains to interact with SCF. (rcsb.org)
  • FMS-like tyrosine kinase 3 ( FLT3 ) is one of the most frequently mutated genes in acute myeloid leukemia (AML). (dovepress.com)
  • Approximately 30% of the adult cases harbor an internal tandem duplication ( FLT3 -ITD) and 5- 10% a tyrosine kinase domain (TKD) amino acid substitution ( FLT3-TKD ). (dovepress.com)
  • Among the most mutated driver genes in AML is FMS-like tyrosine kinase 3 ( FLT3 ). (dovepress.com)
  • Nearly 60% of genetic alterations have been found in AML patients involve in signaling pathways including signaling of tyrosine kinase receptor FLT3. (lu.se)
  • We identified SLAP2 and ABL2 as potent interaction partners of FLT3 through their SH2 domain. (lu.se)
  • Rather, we found that phosphorylated activation loop Y842 serves as a binding site of SHP2, which is required for FLT3-induced activation of RAS/ERK pathway. (lu.se)
  • Wir konnten zeigen, dass in CD22-defizienten B-Zellen nach BZR-Stimulation das Adaptermolekül SLP-65, auch BLNK oder BASH genannt, früher und stärker Tyrosin-phosphoryliert vorliegt, als in Kontroll-B-Zellen. (uni-wuerzburg.de)
  • Jedoch war in den CD22-Transfektanten keine Reduktion der Tyrosin-Phosphorylierung von SLP-65/BLNK nach BZR-Stimulation im Vergleich zu untransfizierten Zellen nachweisbar. (uni-wuerzburg.de)
  • Therefore, the SH2-kinase interface is critical for Btk activation and a targetable site for allosteric inhibition. (rcsb.org)
  • As allosteric interactions provide unique targeting opportunities, we developed an engineered repebody protein binding to the SH2 domain and able to disrupt the SH2-kinase interaction. (rcsb.org)
  • Plexin-B1 has recently been shown to mediate activation of RhoA through a stable interaction with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. (rupress.org)
  • Some functions, such as neutralization, mainly depend on interaction of the Fv domain ( Figure 1A ) with antigen and are therefore predominantly Fc domain independent. (frontiersin.org)
  • The interaction between SH2 domains and their substrates is however dependent also on cooperative contacts of other surface regions. (eu.org)
  • The Src Homology 2 (SH2) domain is a major protein interaction module that is central to tyrosine kinase signaling. (eu.org)
  • Post-translational modifications might contribute to enhanced STAT5 activation in the context of transformation, but the strength and duration of pYSTAT5 are incompletely understood. (nature.com)
  • What is the function of a protein with SRC homology-2 domains? (flashcardmachine.com)
  • Using homology modeling and site-directed mutagenesis, we have localized the RNA-binding surface of the Smaug SAM domain and have elaborated the RNA consensus sequence required for binding. (embl.de)
  • The tyrosine hydroxylase has the homotetrameric structure and contains three diverse structural domains: N-terminal regulatory domain, catalytic domain and C-terminal tetramerization domain [3]. (xray.cz)
  • Since the structure of the regulatory domain is still unknown we decided to perform its structural characterization using NMR techniques. (xray.cz)
  • Structural information illustrated that PRTH-101 interacts with the discoidin (DS)-like domain, but not the collagen-binding DS domain of DDR1. (bvsalud.org)
  • NYU Chemistry Professor Nate Traaseth and colleagues published a study in Nature Chemical Biology called ' Molecular basis for receptor tyrosine kinase A-loop tyrosine transphosphorylation . (nyu.edu)
  • To better understand the molecular changes associated with AD, genome-wide association studies (GWAS) have identified hundreds of candidate genes linked to the disease, like the receptor tyrosine kinase EphA1. (sdbonline.org)
  • Alternative splicing of the avian trkB receptor generates an extracellular deletion (ED) isoform missing 11 amino acids from the neurotrophin-binding domain of the full-length (FL) receptor. (jneurosci.org)
  • The B-Raf protein has 766 amino acids in three conserved domains. (news-medical.net)
  • TCR recognition triggers a complex set of events that result in cellular activation. (harvard.edu)
  • Nevertheless, ex vivo activation with cytokines can restore cytolytic activity of NK cells against GB, indicating that NK cells have potential for adoptive immunotherapy of GB if potent cytotoxicity can be maintained in vivo . (frontiersin.org)
  • 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)
  • CR1 inhibits the activity of CR3, the kinase domain, regulating the overall signaling activity of the molecule. (news-medical.net)
  • This electropositive potential is unique among all previously determined SAM-domain structures and is conserved among Smaug-SAM homologues. (embl.de)
  • The regulatory domain of tyrosine hydroxylase was expressed as six-His-tag fusion protein by IPTG induction for 12 h at 20 C and purified from Escherichia coli BL21(DE3). (xray.cz)
  • Conserved region 1 (CR1) is a Ras-GTP-binding self-regulatory domain. (news-medical.net)
  • Our results indicate that SHP-2 promotes endothelial cell survival and proliferation, possibly by growth factor dependent PI3-K and MAP kinase activation, and is necessary for new vessel formation. (uni-muenchen.de)
  • Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2. (rupress.org)
  • The RNA-binding SAM domain of Smaug defines a new family of post-transcriptional regulators. (embl.de)
  • This represents a new function for the SAM domain family, which is well characterized for mediating protein-protein interactions. (embl.de)
  • Bruton's tyrosine kinase (Btk) is critical for B-cell maturation and activation. (rcsb.org)
  • The CD45 isoforms detected in the mouse are cell type-, maturation-, and activation state-specific. (bdbiosciences.com)
  • A long-standing mystery shrouds the mechanism by which catalytically repressed receptor tyrosine kinase domains accomplish transphosphorylation of activation loop (A-loop) tyrosines. (nyu.edu)
  • The predominant expression pattern of either FL or ED isoforms in single embryonic DRG neurons establishes the existence of two subpopulations exhibiting differential responsiveness to trkB ligands, indicating that regulated splicing of the extracellular domain of trkB may serve as a mechanism to restrict neuronal responsiveness to the neurotrophins. (jneurosci.org)