PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32469452-5 2020 In addition, PTPN22 dephosphorylates EB1 at tyrosine-247 (Y247), which decreases the expression of the T-cell activation markers CD25 and CD69 and the phosphorylation levels of the TCR molecules ZAP-70, LAT, and Erk, leading to the eventual downregulation of the transcription factor NFAT and reduced the levels of secreted IL-2. Tyrosine 44-52 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 195-201 33562083-2 2021 Proper TCR signaling requires the sequential activities of Lck and ZAP-70 kinases, which result in the phosphorylation of tyrosine residues located in the CD3 ITAMs and the LAT adaptor, respectively. Tyrosine 122-130 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 67-73 32238854-3 2021 In this study, we demonstrate that IMiDs also directly bind and activate zeta-chain-associated protein kinase-70 (Zap-70) via its tyrosine residue phosphorylation in T cells. Tyrosine 130-138 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 73-112 32238854-3 2021 In this study, we demonstrate that IMiDs also directly bind and activate zeta-chain-associated protein kinase-70 (Zap-70) via its tyrosine residue phosphorylation in T cells. Tyrosine 130-138 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 114-120 31964936-3 2020 Results revealed that the activity of various tyrosine kinases of the FGFR family and ZAP70 was increased, whereas the activity of multiple Ser/Thr kinases such as IKKalpha, CaMK4, PKAalpha, PKCalpha+delta (among others) was decreased in lymphocytes of endurance trained athletes (ET). Tyrosine 46-54 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 86-91 29789296-2 2018 To convert this binding event into downstream signaling, the TCR complex contains immunoreceptor tyrosine-based activation motifs (ITAMs) that act as docking sites for the cytoplasmic tyrosine kinase ZAP-70. Tyrosine 97-105 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 200-206 30372858-2 2018 As a 56 KDa protein, Lck phosphorylates tyrosine residues of various proteins such as ZAP-70, ITK and protein kinase C. The structure of Lck is comprised of three domains, one SH3 in tandem with a SH2 domain at the amino terminal and the kinase domain at the carboxy terminal. Tyrosine 40-48 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 86-92 25682964-5 2015 We demonstrated that phosphorylation of SYK and LYN, key B-cell receptor signaling kinases, was independent of PD-1 expression in patients with CLL, while ZAP-70 phosphorylation in negative tyrosine residue 292 showed strong inverse correlation (r = - 0.8, p = 0.0019). Tyrosine 190-198 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 155-161 28415650-5 2017 It is well-established that the activity/expression of Zap70 is regulated by post-translational modifications of crucial amino acids including the phosphorylation of tyrosines and the ubiquitination of lysines. Tyrosine 166-175 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 55-60 25990959-4 2015 The data indicated that the kinase activity of ZAP-70 stimulates negative feedback pathways that target Lck and thereby modulate the phosphorylation patterns of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the CD3 and zeta chain components of the TCR and of signaling molecules downstream of Lck, including ZAP-70. Tyrosine 180-188 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 47-53 25990959-4 2015 The data indicated that the kinase activity of ZAP-70 stimulates negative feedback pathways that target Lck and thereby modulate the phosphorylation patterns of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the CD3 and zeta chain components of the TCR and of signaling molecules downstream of Lck, including ZAP-70. Tyrosine 180-188 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 325-331 25990959-6 2015 This model incorporated negative feedback regulation of Lck activity by the kinase activity of ZAP-70 and predicted the order in which tyrosines in the ITAMs of TCR zeta chains must be phosphorylated to be consistent with the experimental data. Tyrosine 135-144 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 95-101 25800872-4 2015 ctSLAPDeltaC inhibited tyrosine phosphorylation of signaling mediators such as ZAP-70 and LAT involved in T cell activation, and effectively suppressed transcriptional activity of NFAT and NFkappaB upon TcR stimulation. Tyrosine 23-31 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 79-85 26043137-4 2015 Importantly, this study revealed a new function for Vav1 in the negative feedback regulation of the phosphorylation of immunoreceptor tyrosine-based activation motifs within the zeta chains, CD3 delta, epsilon, gamma chains, as well as activation sites on the critical T cell tyrosine kinases Itk, Lck, and ZAP-70. Tyrosine 134-142 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 307-313 24204825-0 2013 Quantitative phosphoproteome analysis unveils LAT as a modulator of CD3zeta and ZAP-70 tyrosine phosphorylation. Tyrosine 87-95 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 80-86 25316710-7 2015 In addition, N-terminal tyrosine sites of SLP-76 also perturbed phosphorylation of Tyr(440) of Fyn, Tyr(702) of PLCgamma1, Tyr(204), Tyr(397), and Tyr(69) of ZAP-70, revealing new modes of regulation on these sites. Tyrosine 24-32 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 158-164 24256567-7 2014 Sts-1 substrate-trapping mutants isolated tyrosine-phosphorylated Zap-70 from lysates of activated T cells, validating Zap-70 as a possible substrate for Sts-1 and highlighting the efficacy of the mutants as substrate-trapping agents. Tyrosine 42-50 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 66-72 24256567-7 2014 Sts-1 substrate-trapping mutants isolated tyrosine-phosphorylated Zap-70 from lysates of activated T cells, validating Zap-70 as a possible substrate for Sts-1 and highlighting the efficacy of the mutants as substrate-trapping agents. Tyrosine 42-50 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 119-125 23124046-3 2013 ZAP70, one of those PTKs, is a 70-kDa tyrosine phosphoprotein and associates with the zeta chain and undergoes tyrosine phosphorylation following TCR stimulation. Tyrosine 38-46 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-5 23874979-6 2013 Although the majority of identified sites on T cell receptor signaling proteins showed decreases in phosphorylation, Tyr(598) of ZAP-70 showed elevated phosphorylation in response to U0126 treatment, suggesting differential regulation of this site via ERK feedback. Tyrosine 117-120 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 129-135 23530057-2 2013 We previously reported the structure of an autoinhibited ZAP-70 variant in which two regulatory tyrosine residues (315 and 319) in the SH2-kinase linker were replaced by phenylalanine. Tyrosine 96-104 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 57-63 23530057-3 2013 We now present a crystal structure of ZAP-70 in which Tyr 315 and Tyr 319 are not mutated, leading to the recognition of a five-residue sequence register error in the SH2-kinase linker of the original crystallographic model. Tyrosine 54-57 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 38-44 23530057-3 2013 We now present a crystal structure of ZAP-70 in which Tyr 315 and Tyr 319 are not mutated, leading to the recognition of a five-residue sequence register error in the SH2-kinase linker of the original crystallographic model. Tyrosine 66-69 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 38-44 23530057-5 2013 As seen in a recently reported structure of the related tyrosine kinase Syk, Tyr 315 of ZAP-70 is part of a hydrophobic interface between the regulatory apparatus and the kinase domain, and the integrity of this interface would be lost upon engagement of doubly phosphorylated peptides by the SH2 domains. Tyrosine 77-80 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 88-94 23530057-6 2013 Tyr 319 is not necessarily dislodged by SH2 engagement, which activates ZAP-70 only ~5-fold in vitro. Tyrosine 0-3 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 72-78 23530057-8 2013 This difference is due to the ability of Tyr 319 to suppress ZAP-70 activity even when the SH2 domains are dislodged from the kinase domain, providing stringent control of ZAP-70 activity downstream of Lck. Tyrosine 41-44 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 61-67 23530057-8 2013 This difference is due to the ability of Tyr 319 to suppress ZAP-70 activity even when the SH2 domains are dislodged from the kinase domain, providing stringent control of ZAP-70 activity downstream of Lck. Tyrosine 41-44 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 172-178 23880762-6 2013 We report that overexpression of Mn-SOD enhances tyrosine phosphorylation of TCR-associated membrane proximal signal transduction molecules Lck, LAT, ZAP70, PLCgamma1, and SLP76 within 1 min of TCR cross-linking. Tyrosine 49-57 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 150-155 21725281-6 2011 In intact cells, Y173 phosphorylation depended on three, ZAP-70-targeted tyrosines at the N-terminus of SLP-76 that recruit and activate Itk, a kinase that selectively phosphorylated Y173 in vitro. Tyrosine 73-82 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 57-63 22207134-0 2012 Fine-tuning of proximal TCR signaling by ZAP-70 tyrosine residues in Jurkat cells. Tyrosine 48-56 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 41-47 21757751-5 2011 After CD5 ligation, phosphorylation of the negative regulatory tyrosine (Tyr(531)) of Fyn increases, and this correlates with a substantial reduction in the kinase activity of Fyn and a profound inhibition of ZAP-70 activation. Tyrosine 63-71 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 209-215 21757751-5 2011 After CD5 ligation, phosphorylation of the negative regulatory tyrosine (Tyr(531)) of Fyn increases, and this correlates with a substantial reduction in the kinase activity of Fyn and a profound inhibition of ZAP-70 activation. Tyrosine 73-76 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 209-215 22898186-0 2013 ZAP-70 tyrosines 315 and 492 transmit non-genomic glucocorticoid (GC) effects in T cells. Tyrosine 7-16 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 22898186-3 2013 In the present work, first, we identified those tyrosine (Y) residues of the ZAP-70 kinase which were involved in non-genomic GC signaling using an array of P116 cells (ZAP-70-deficient Jurkat subclone) lentivirally-transfected with wild type or point-mutated ZAP-70 constructs where Y-residues were replaced with phenylalanine (F) at positions 069, 126, 178, 238, 292, 315, 492 or 493. Tyrosine 48-56 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 77-83 22898186-3 2013 In the present work, first, we identified those tyrosine (Y) residues of the ZAP-70 kinase which were involved in non-genomic GC signaling using an array of P116 cells (ZAP-70-deficient Jurkat subclone) lentivirally-transfected with wild type or point-mutated ZAP-70 constructs where Y-residues were replaced with phenylalanine (F) at positions 069, 126, 178, 238, 292, 315, 492 or 493. Tyrosine 48-56 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 169-175 22898186-3 2013 In the present work, first, we identified those tyrosine (Y) residues of the ZAP-70 kinase which were involved in non-genomic GC signaling using an array of P116 cells (ZAP-70-deficient Jurkat subclone) lentivirally-transfected with wild type or point-mutated ZAP-70 constructs where Y-residues were replaced with phenylalanine (F) at positions 069, 126, 178, 238, 292, 315, 492 or 493. Tyrosine 48-56 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 169-175 21463338-8 2011 Ethanol decreases tyrosine phosphorylation and activation of upstream signaling proteins PLCgamma1, LAT, ZAP70, and Lck. Tyrosine 18-26 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 105-110 21393235-8 2011 Here, we demonstrate that Sts-2 regulates the level of tyrosine phosphorylation on targets within T cells, among them the critical T cell tyrosine kinase Zap-70. Tyrosine 55-63 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 154-160 19290920-1 2009 The tyrosine ZAP-70 (zeta-associated protein of 70 kDa) kinase plays a critical role in activating many downstream signal transduction pathways in T cells following T-cell receptor (TCR) engagement. Tyrosine 4-12 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 13-19 20682913-4 2010 Transient or stable knockdown of Duox1 inhibited TCR signaling, especially phosphorylation of tyrosine-319 of zeta chain-associated protein kinase of 70 kilodaltons (ZAP-70), store-operated entry of calcium ions (Ca(2+)), and activation of extracellular signal-regulated kinase. Tyrosine 94-102 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 166-172 19168706-5 2009 In T cells, ZAP-70 phosphorylation is dependent on lymphocyte-specific protein tyrosine kinase (Lck) activity, which in turn is either positively or negatively regulated by the phosphorylation of specific Lck tyrosine residues. Tyrosine 79-87 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 12-18 19605366-5 2009 We have combined genetic analysis with quantitative proteomic methods and recently developed visual analysis tools to dissect the tyrosine phosphoproteome of isogenic Zap-70 tyrosine kinase null and reconstituted Jurkat T cells. Tyrosine 130-138 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 167-173 19290920-1 2009 The tyrosine ZAP-70 (zeta-associated protein of 70 kDa) kinase plays a critical role in activating many downstream signal transduction pathways in T cells following T-cell receptor (TCR) engagement. Tyrosine 4-12 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 21-54 18548611-10 2008 The phosphorylation of these ZAP70 tyrosine residues cells was blocked by an Lck inhibitor, suggesting the existence of an Lck-coupled truncated ZAP70 protein or a novel isoform of ZAP70 in P116 cells. Tyrosine 35-43 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 29-34 18548611-10 2008 The phosphorylation of these ZAP70 tyrosine residues cells was blocked by an Lck inhibitor, suggesting the existence of an Lck-coupled truncated ZAP70 protein or a novel isoform of ZAP70 in P116 cells. Tyrosine 35-43 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 145-150 18548611-10 2008 The phosphorylation of these ZAP70 tyrosine residues cells was blocked by an Lck inhibitor, suggesting the existence of an Lck-coupled truncated ZAP70 protein or a novel isoform of ZAP70 in P116 cells. Tyrosine 35-43 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 145-150 18432193-5 2008 Here we show that Drosophila Shark, a non-receptor tyrosine kinase similar to mammalian Syk and Zap-70, binds Draper through an immunoreceptor tyrosine-based activation motif (ITAM) in the Draper intracellular domain. Tyrosine 51-59 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 96-102 17579062-4 2007 Analysis of key upstream events such as Zap70 phosphorylation showed that modulation of Tyr(292) and Tyr(319) phosphorylation occurred concomitantly with 13B8.2-induced Zap70 exclusion from the membrane rafts. Tyrosine 88-91 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 40-45 18287138-6 2008 In the cohort studies, surface IgM-induced protein tyrosine phosphorylation correlated significantly with CD38 and ZAP-70 expression and with the absence of Ig VH gene mutations. Tyrosine 51-59 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 115-121 18092677-4 2007 Mutational analyses showed that this ITAM-like sequence was a substrate for the Src family kinase Fyn, and two conserved tyrosine residues were required for coprecipitating Lyn, Syk, and ZAP-70 kinases. Tyrosine 121-129 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 187-193 17222799-2 2007 Previously, we have shown that high dose Dexamethasone (DX) treatment of Jurkat cells causes tyrosine phosphorylation of ZAP-70 within 5 min in a GR-dependent manner. Tyrosine 93-101 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 121-127 17250586-6 2007 ZAP-70 was phosphorylated on tyrosine 319, LAT on tyrosines 171 and 191, and PLCgamma1 on tyrosine 783. Tyrosine 29-37 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 17250586-6 2007 ZAP-70 was phosphorylated on tyrosine 319, LAT on tyrosines 171 and 191, and PLCgamma1 on tyrosine 783. Tyrosine 50-59 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 17250586-6 2007 ZAP-70 was phosphorylated on tyrosine 319, LAT on tyrosines 171 and 191, and PLCgamma1 on tyrosine 783. Tyrosine 50-58 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 17250586-7 2007 The ZAP-70 inhibitor piceatannol reduced CXCR3-mediated tyrosine phosphorylation of ZAP-70, LAT, PLCgamma1 and mitogen-activated protein kinase Erk and it reduced CXCL10-mediated chemotaxis of both CXCR3-transfected Jurkat T cells and normal T cells expressing CXCR3. Tyrosine 56-64 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 4-10 17250586-7 2007 The ZAP-70 inhibitor piceatannol reduced CXCR3-mediated tyrosine phosphorylation of ZAP-70, LAT, PLCgamma1 and mitogen-activated protein kinase Erk and it reduced CXCL10-mediated chemotaxis of both CXCR3-transfected Jurkat T cells and normal T cells expressing CXCR3. Tyrosine 56-64 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 84-90 17512407-1 2007 ZAP-70, a cytoplasmic tyrosine kinase required for T cell antigen receptor signaling, is controlled by a regulatory segment that includes a tandem SH2 unit responsible for binding to immunoreceptor tyrosine-based activation motifs (ITAMs). Tyrosine 22-30 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 17512407-4 2007 Two tyrosine residues in the SH2-kinase linker that activate ZAP-70 when phosphorylated are involved in aromatic-aromatic interactions that connect the linker to the kinase domain. Tyrosine 4-12 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 61-67 17250586-8 2007 These results are consistent with the involvement of ZAP-70 in CXCR3-mediated protein tyrosine phosphorylation and CXCR3-induced T-cell chemotaxis. Tyrosine 86-94 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 53-59 16461343-8 2006 Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Tyrosine 65-73 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 39-44 17038529-4 2007 We have now compared antigen receptor-induced activation of ZAP-70 in B cells and T cells by analyzing phosphorylation of critical regulatory tyrosine residues. Tyrosine 142-150 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 60-66 16461343-8 2006 Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Tyrosine 95-98 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 39-44 16461343-8 2006 Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Tyrosine 95-98 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 39-44 16984412-6 2006 However, TCR-mediated NFAT activation and tyrosine phosphorylation of zeta-associated protein 70 (Zap-70) were inhibited in cells pre-stimulated by flagellin. Tyrosine 42-50 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 70-96 16984412-6 2006 However, TCR-mediated NFAT activation and tyrosine phosphorylation of zeta-associated protein 70 (Zap-70) were inhibited in cells pre-stimulated by flagellin. Tyrosine 42-50 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 98-104 16461343-8 2006 Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Tyrosine 83-86 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 39-44 16461343-8 2006 Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Tyrosine 95-98 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 39-44 16219325-6 2005 We first demonstrate that ZAP70 plays a pivotal role in interferon-stimulated MAPK activation, and that the tyrosine residue at position 319 of ZAP70 is important for interferon-stimulated ERK activation. Tyrosine 108-116 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 144-149 16406604-0 2006 Dexamethasone induces rapid tyrosine-phosphorylation of ZAP-70 in Jurkat cells. Tyrosine 28-36 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 56-62 16406604-7 2006 Here, we demonstrate that high dose DX induced a rapid ZAP-70 tyrosine-phosphorylation in Jurkat T-cells. Tyrosine 62-70 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 55-61 16339550-0 2005 T cell activation-induced CrkII binding to the Zap70 protein tyrosine kinase is mediated by Lck-dependent phosphorylation of Zap70 tyrosine 315. Tyrosine 61-69 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 47-52 16339550-0 2005 T cell activation-induced CrkII binding to the Zap70 protein tyrosine kinase is mediated by Lck-dependent phosphorylation of Zap70 tyrosine 315. Tyrosine 61-69 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 125-130 16339550-2 2005 Following engagement of TCR, the Zap70 undergoes phosphorylation on multiple tyrosine residues that are implicated in the regulation of its catalytic activity and interaction with signaling effector molecules downstream of the TCR. Tyrosine 77-85 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 33-38 16339550-3 2005 We have shown previously that the CT10 regulator of kinase II (CrkII) adapter protein interacts with tyrosine-phosphorylated Zap70 in TCR-engaged T cells, and now extend these studies to show that Tyr315 in the Zap70 interdomain B region is the site of interaction with CrkII. Tyrosine 101-109 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 125-130 16339550-3 2005 We have shown previously that the CT10 regulator of kinase II (CrkII) adapter protein interacts with tyrosine-phosphorylated Zap70 in TCR-engaged T cells, and now extend these studies to show that Tyr315 in the Zap70 interdomain B region is the site of interaction with CrkII. Tyrosine 101-109 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 211-216 16081816-6 2005 In additions, we provide evidence that ZAP-70 is the primary in vivo kinase for LAT tyrosine 191 and that Itk plays a role in the phosphorylation of tyrosine 783 on phospholipase C-gamma1. Tyrosine 149-157 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 39-45 16151467-5 2005 Furthermore, IM therapy at clinical doses suppressed the tyrosine phosphorylation of ZAP70. Tyrosine 57-65 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 85-90 16049944-1 2005 The protein kinase ZAP-70 is involved in T-cell activation and interacts with tyrosine-phosphorylated peptide sequences known as immunoreceptor tyrosine activation motifs (ITAMs). Tyrosine 78-86 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 19-25 16049944-1 2005 The protein kinase ZAP-70 is involved in T-cell activation and interacts with tyrosine-phosphorylated peptide sequences known as immunoreceptor tyrosine activation motifs (ITAMs). Tyrosine 144-152 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 19-25 16081816-6 2005 In additions, we provide evidence that ZAP-70 is the primary in vivo kinase for LAT tyrosine 191 and that Itk plays a role in the phosphorylation of tyrosine 783 on phospholipase C-gamma1. Tyrosine 84-92 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 39-45 15307176-7 2004 CD46 enhanced TCR/CD3-induced tyrosine phosphorylation of CD3zeta and ZAP-70, as well as the activation of the ERK, JNK, and p38, but did not modify intracellular calcium. Tyrosine 30-38 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 70-76 15832176-0 2005 Role of p56lck and ZAP70-mediated tyrosine phosphorylation in galectin-1-induced cell death. Tyrosine 34-42 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 19-24 15572591-7 2005 Analysis of the TCR-induced signaling cascade showed that imatinib substantially reduced tyrosine phosphorylation of ZAP70 and LAT in response to activation through the TCR. Tyrosine 89-97 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 117-122 15749915-6 2005 For subgroup IIb cells, based on tyrosine phosphorylation and translocation into lipid rafts, sIgM signaling was shown to be enhanced by Zap70. Tyrosine 33-41 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 137-142 15292186-4 2004 The crystal structure shows that this ZAP-70 kinase domain is in an active-like conformation despite the lack of tyrosine phosphorylation in the activation loop. Tyrosine 113-121 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 38-44 15050291-6 2004 Lowered tyrosine phosphorylation of IkappaBalpha may be due to a decrease in activity of p56(lck) and ZAP-70, since treatment with piceatannol, an inhibitor of syk and src family kinases, mimics age associated decline in tyrosine phosphorylation of IkappaBalpha in T cells from young donors. Tyrosine 8-16 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 102-108 15100278-5 2004 These mutations in the ZAP-70 interdomain B region also specifically affect CD3/TCR-mediated tyrosine phosphorylation of residues 171 and 191 in the cytoplasmic domain of the linker for activation of T cells (LAT) adapter protein. Tyrosine 93-101 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 23-29 15100278-8 2004 Thus, these studies demonstrate that the interdomain B region of ZAP-70 regulates beta(1) integrin activation by the CD3/TCR via control of tyrosine phosphorylation of tyrosine residues 171 and 191 in the LAT cytoplasmic domain. Tyrosine 140-148 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 65-71 15100278-8 2004 Thus, these studies demonstrate that the interdomain B region of ZAP-70 regulates beta(1) integrin activation by the CD3/TCR via control of tyrosine phosphorylation of tyrosine residues 171 and 191 in the LAT cytoplasmic domain. Tyrosine 168-176 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 65-71 15059847-9 2004 Importantly, the presence of ZAP-70 positively regulates the TCR-induced tyrosine phosphorylation of Syk. Tyrosine 73-81 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 29-35 14557276-7 2003 ZAP-70 phosphorylated HIP-55 at Tyr-334 and Tyr-344 in vitro and in vivo, and the HIP-55 mutant (Y334F/Y344F) was not tyrosine-phosphorylated in stimulated T cells. Tyrosine 32-35 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 12417718-2 2002 There are three conserved tyrosines in this linker region; Tyr317 of Syk and its equivalent residue in ZAP70 were previously shown to negatively regulate the function of Syk and ZAP70. Tyrosine 26-35 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 103-108 12447358-0 2003 Tyrosine phosphorylation of VHR phosphatase by ZAP-70. Tyrosine 0-8 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 47-53 12845584-10 2003 Four forms of the ZAP-70 peptide ALGADDSYYTAR with both, either or neither tyrosine phosphorylated were subjected to a 0-1.5 V potential ramp. Tyrosine 75-83 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 18-24 12817019-5 2003 This pathway involves ZAP-70-dependent tyrosine phosphorylation of SLP-76 at one or more of its tyrosines, 113, 128, and 145. Tyrosine 39-47 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 22-28 12817019-5 2003 This pathway involves ZAP-70-dependent tyrosine phosphorylation of SLP-76 at one or more of its tyrosines, 113, 128, and 145. Tyrosine 96-105 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 22-28 12393534-5 2002 Ligation of the B-cell receptor (BCR) complex on CLL cells that expressed ZAP-70 induced significantly greater tyrosine phosphorylation of cytosolic proteins, including p72(Syk), than did similar stimulation of CLL cells that did not express ZAP-70. Tyrosine 111-119 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 74-80 12393534-6 2002 Also, exceptional cases of CLL cells that expressed mutated immunoglobulin V genes and ZAP-70 also experienced higher levels tyrosine phosphorylation of such cytosolic proteins following BCR ligation. Tyrosine 125-133 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 87-93 12393534-7 2002 Following BCR ligation, ZAP-70 underwent tyrosine phosphorylation and became associated with surface immunoglobulin and CD79b, arguing for the involvement of ZAP-70 in BCR signaling. Tyrosine 41-49 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 24-30 12450381-1 2002 The protein kinase ZAP-70 is involved in T-cell activation, and interacts with tyrosine-phosphorylated peptide sequences known as immunoreceptor tyrosine activation motifs (ITAMs), which are present in three of the subunits of the T-cell receptor. Tyrosine 79-87 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 19-25 12450381-1 2002 The protein kinase ZAP-70 is involved in T-cell activation, and interacts with tyrosine-phosphorylated peptide sequences known as immunoreceptor tyrosine activation motifs (ITAMs), which are present in three of the subunits of the T-cell receptor. Tyrosine 145-153 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 19-25 12417718-2 2002 There are three conserved tyrosines in this linker region; Tyr317 of Syk and its equivalent residue in ZAP70 were previously shown to negatively regulate the function of Syk and ZAP70. Tyrosine 26-35 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 178-183 11970985-0 2002 CTLA-4 suppresses proximal TCR signaling in resting human CD4(+) T cells by inhibiting ZAP-70 Tyr(319) phosphorylation: a potential role for tyrosine phosphatases. Tyrosine 94-97 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 87-93 11976341-0 2002 Activation of ZAP-70 through specific dephosphorylation at the inhibitory Tyr-292 by the low molecular weight phosphotyrosine phosphatase (LMPTP). Tyrosine 74-77 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 14-20 11976341-2 2002 Recruitment and activation of ZAP-70 are transient and are terminated by phosphorylation of negative regulatory tyrosine residues and dephosphorylation of positively acting sites. Tyrosine 112-120 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 30-36 11976341-3 2002 We report that the low molecular weight protein-tyrosine phosphatase (LMPTP) specifically dephosphorylates the negative regulatory Tyr-292 of ZAP-70, thereby counteracting inactivation of ZAP-70. Tyrosine 131-134 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 142-148 11976341-3 2002 We report that the low molecular weight protein-tyrosine phosphatase (LMPTP) specifically dephosphorylates the negative regulatory Tyr-292 of ZAP-70, thereby counteracting inactivation of ZAP-70. Tyrosine 131-134 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 188-194 11976341-4 2002 Expression of low levels of LMPTP resulted in increased ZAP-70 phosphorylation, presumably at the activating Tyr-493 and other sites, increased kinase activity, and augmented downstream signaling to the mitogen-activated protein kinase pathway. Tyrosine 109-112 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 56-62 12051764-6 2002 Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Tyrosine 0-8 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 109-114 12351398-3 2002 We show that coengagement of T-cell receptor (TCR) and CD158a by tumor cells inhibited tyrosine phosphorylation of early signaling proteins ZAP-70 and LAT, lipid raft coalescence, and TCR/CD3 accumulation at the CTL/tumor cell interface. Tyrosine 87-95 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 140-146 11981413-9 2002 Finally, partial or complete tyrosine phosphorylation of Zap70 was observed in alloantigen-specific T cell clones in response to tolerogenic versus immunogenic peptides, respectively. Tyrosine 29-37 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 57-62 11786178-5 2001 2/ The phospho-peptide induced tyrosine phosphorylation events were at least partially mediated by p56(lck) and Syk/ZAP70 protein tyrosine kinases as it was shown in p56(lck) and Syk/ZAP70 deficient Jurkat variants. Tyrosine 31-39 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 116-121 11744042-0 2002 Effect of age and oxidative stress on tyrosine phosphorylation of ZAP-70. Tyrosine 38-46 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 66-72 11744042-3 2002 The present study was carried out to determine the effect of reactive oxygen species on tyrosine phosphorylation of ZAP-70, a key enzyme in the T-cell signal transduction pathway. Tyrosine 88-96 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 116-122 11744042-4 2002 Our previous as well as present studies have demonstrated an age-related down-regulation of tyrosine phosphorylation of ZAP-70 following activation of freshly isolated T cells with various stimulating agents. Tyrosine 92-100 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 120-126 11744042-5 2002 Currently, we observe that under mild and chronic oxidative stress, tyrosine phosphorylation of ZAP-70 is impaired following stimulation of the T cells with anti-CD3 antibody. Tyrosine 68-76 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 96-102 11744042-7 2002 The current observation suggests that the age-associated down-regulation of tyrosine phosphorylation of ZAP-70 is not an intrinsic defect inherent of the T cells due to aging and is reversible. Tyrosine 76-84 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 104-110 11744042-9 2002 Finally, it was also noted that the down-regulation of tyrosine phosphorylation of ZAP-70 under oxidative stress in young and elderly donors was not due to impairment in the net expression of ZAP-70 under oxidative stress thereby suggesting that dysregulation in the balance of kinase-phosphatase activities under oxidative stress might have been implicated in the observed phenomenon. Tyrosine 55-63 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 83-89 11849313-6 2002 Activation of PARs also led to an increase in tyrosine phosphorylation of ZAP-70 and SLP-76, two key proteins in T-cell receptor (TCR) signalling. Tyrosine 46-54 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 74-80 11855827-2 2002 Thus, phenylalanine substitution at the N-terminal tyrosine residue of the CD3-epsilon-ITAM abolished signal transduction functions of this ITAM, including phosphorylation at the C-terminal ITAM tyrosine, and its association with ZAP-70. Tyrosine 51-59 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 230-236 11786178-5 2001 2/ The phospho-peptide induced tyrosine phosphorylation events were at least partially mediated by p56(lck) and Syk/ZAP70 protein tyrosine kinases as it was shown in p56(lck) and Syk/ZAP70 deficient Jurkat variants. Tyrosine 31-39 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 183-188 11420038-3 2001 Whereas the inducible tyrosine phosphorylation of TCR zeta and ZAP-70 and the kinase activity of Lck were intact, phosphorylated LAT was rapidly dephosphorylated by raft targeting of activated SHP-1, leading to defects in LAT activation and subsequent downstream signaling events. Tyrosine 22-30 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 63-69 11489961-5 2001 The tyrosine residue at position 292 in the interdomain B region of ZAP-70 exerts a negative regulatory effect on ZAP-70-dependent migration. Tyrosine 4-12 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 68-74 11489961-5 2001 The tyrosine residue at position 292 in the interdomain B region of ZAP-70 exerts a negative regulatory effect on ZAP-70-dependent migration. Tyrosine 4-12 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 114-120 11489961-6 2001 Stimulation of Jurkat T cells with CXCL12 also resulted in ZAP-70-dependent tyrosine phosphorylation of the Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) adapter protein. Tyrosine 76-84 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 59-65 11368773-3 2001 In the present study we reconstituted the LAT signalling pathway by demonstrating that a direct tyrosine phosphorylation of LAT with activated protein-tyrosine kinase Zap70 is necessary and sufficient for the association and activation of signalling proteins. Tyrosine 96-104 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 167-172 11368773-4 2001 Zap-70 efficiently phosphorylates LAT on tyrosine residues at positions 226, 191, 171, 132 and 127. Tyrosine 41-49 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 11418612-1 2001 The Crk adapter proteins are assumed to play a role in T lymphocyte activation because of their induced association with tyrosine-phosphorylated proteins, such as ZAP-70 and Cbl, and with the phosphatidylinositol 3kinase regulatory subunit, p85, following engagement of the T cell antigen receptor. Tyrosine 121-129 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 163-169 11418612-2 2001 Although the exact mechanism of interaction between these molecules has not been fully defined, it has been generally accepted that Crk, ZAP-70, and p85 interact with tyrosine-phosphorylated Cbl, which serves as a major scaffold protein in activated T lymphocytes. Tyrosine 167-175 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 137-143 11509614-8 2001 Mechanistic studies revealed that CD3zeta and ZAP-70 were more heavily tyrosine phosphorylated in J45.01 cells than Jurkat cells. Tyrosine 71-79 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 46-52 11514606-2 2001 Phosphorylation of Tyr 493 within ZAP-70"s activation loop results in the enzymatic activation of ZAP-70. Tyrosine 19-22 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 34-40 11514606-2 2001 Phosphorylation of Tyr 493 within ZAP-70"s activation loop results in the enzymatic activation of ZAP-70. Tyrosine 19-22 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 98-104 11514606-3 2001 Additional tyrosines (Tyrs) within ZAP-70 are phosphorylated that play both positive and negative regulatory roles in TCR function. Tyrosine 11-20 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 35-41 11514606-3 2001 Additional tyrosines (Tyrs) within ZAP-70 are phosphorylated that play both positive and negative regulatory roles in TCR function. Tyrosine 22-26 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 35-41 11514606-4 2001 Phosphorylation of Tyr residues (Tyrs 315 and 319) within the Interdomain B region of the ZAP-70 PTK plays important roles in the generation of second messengers after TCR engagement. Tyrosine 19-22 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 90-96 11514606-4 2001 Phosphorylation of Tyr residues (Tyrs 315 and 319) within the Interdomain B region of the ZAP-70 PTK plays important roles in the generation of second messengers after TCR engagement. Tyrosine 33-37 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 90-96 11046020-7 2000 Interestingly, a ZAP-70 mutant with a tyrosine to phenylalanine substitution at position 319 (Y319F) restored the adhesive defect in P116 T cells, even though Y319F ZAP-70 failed to fully reconstitute CD3-initiated NF-AT-dependent transcription and tyrosine phosphorylation of the LAT adapter protein. Tyrosine 38-46 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 17-23 11270871-6 2001 Application of the method was extended to identify phosphopeptides generated from a trypsin digest of recombinant autophosphorylated ZAP-70, in particular with respect to quantifying the status at the regulatory phosphorylation sites Tyr-492 and Tyr-493. Tyrosine 234-237 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 133-139 11270871-6 2001 Application of the method was extended to identify phosphopeptides generated from a trypsin digest of recombinant autophosphorylated ZAP-70, in particular with respect to quantifying the status at the regulatory phosphorylation sites Tyr-492 and Tyr-493. Tyrosine 246-249 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 133-139 11279207-4 2001 Co-expression of protein-tyrosine kinases, Lck and Zap70, with HPK1 led to HPK1 activation and tyrosine phosphorylation in transfected mammalian cells. Tyrosine 25-33 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 51-56 11283153-4 2001 We demonstrate in this work that dexamethasone, a synthetic GC, inhibits the early signaling events initiated upon TCR ligation, such as tyrosine phosphorylation of several TCR-associated substrates including the zeta chain, the ZAP70 kinase, and the transmembrane adapter molecule linker for activation of T cells. Tyrosine 137-145 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 229-234 11015446-6 2000 Activation of the Syk/ZAP70 tyrosine kinases by the immunoreceptor tyrosine-based activation motif-containing DAP12 adaptor and of the phosphatidylinositol 3-kinase pathway by the YxNM-containing DAP10 adaptor may play an important role in the stimulation of NK cells and T cells. Tyrosine 28-36 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 22-27 10709104-8 2000 Consistent with these findings, CEA-specific CTL showed increased tyrosine phosphorylation of TCR signaling proteins ZAP-70 and TCR zeta chains in response to both peptides. Tyrosine 66-74 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 117-123 11090635-2 2000 By screening more than 6 billion peptides oriented by a common Tyr residue for their ability to bind to ZAP-70, we determined a consensus optimal peptide. Tyrosine 63-66 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 104-110 10979964-5 2000 Using Jurkat cell lines deficient in ZAP70/Syk (P116) or LAT (ANJ3) expression, CD2-dependent PLCgamma-1 and SLP-76 tyrosine phosphorylation required expression both of ZAP70 or Syk and of LAT. Tyrosine 116-124 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 37-42 10979964-5 2000 Using Jurkat cell lines deficient in ZAP70/Syk (P116) or LAT (ANJ3) expression, CD2-dependent PLCgamma-1 and SLP-76 tyrosine phosphorylation required expression both of ZAP70 or Syk and of LAT. Tyrosine 116-124 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 169-174 10681590-4 2000 The subsequent tyrosine phosphorylation of LAT (linker for activation of T cell) by ZAP-70 leads to a shift in equilibrium from the ZAP-70.Grb-2.SOS(Vav) complex to the (Vav)SOS.Grb-2.LAT complex. Tyrosine 15-23 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 84-90 10704231-0 2000 Activation of Zap-70 tyrosine kinase due to a structural rearrangement induced by tyrosine phosphorylation and/or ITAM binding. Tyrosine 21-29 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 14-20 10704231-2 2000 Binding of ZAP-70 to the phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR zeta chain through its two src-homology 2 (SH2) domains results in its activation coupled to phosphorylation on multiple tyrosine residues, mediated by Src kinases including Lck as well as by autophosphorylation. Tyrosine 55-63 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 11-17 10704231-2 2000 Binding of ZAP-70 to the phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR zeta chain through its two src-homology 2 (SH2) domains results in its activation coupled to phosphorylation on multiple tyrosine residues, mediated by Src kinases including Lck as well as by autophosphorylation. Tyrosine 228-236 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 11-17 10704231-8 2000 The same results were obtained using a ZAP-70 mutant lacking the interdomain B tyrosines. Tyrosine 79-88 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 39-45 10704231-9 2000 These findings are consistent with a mechanism in which ZAP-70 phosphorylation/autophosphorylation on tyrosine(s) other than 292, 315, and 319, as well as engagement of the SH2 domains by the phosphorylated TCR, can induce a conformational change leading to accelerated enzyme kinetics and higher catalytic efficiency. Tyrosine 102-110 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 56-62 10681590-4 2000 The subsequent tyrosine phosphorylation of LAT (linker for activation of T cell) by ZAP-70 leads to a shift in equilibrium from the ZAP-70.Grb-2.SOS(Vav) complex to the (Vav)SOS.Grb-2.LAT complex. Tyrosine 15-23 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 132-138 10604992-4 2000 Here, we show that sole TCR ligation induces zeta-associated protein (ZAP)-70-dependent tyrosine phosphorylation of CTLA-4 that is important for cell surface retention of this molecule. Tyrosine 88-96 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 45-77 10648627-2 2000 They are responsible for the initial tyrosine phosphorylation of the receptor, leading to the recruitment of the ZAP-70 tyrosine kinase, as well as the subsequent phosphorylation and activation of ZAP-70. Tyrosine 37-45 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 113-119 10648627-2 2000 They are responsible for the initial tyrosine phosphorylation of the receptor, leading to the recruitment of the ZAP-70 tyrosine kinase, as well as the subsequent phosphorylation and activation of ZAP-70. Tyrosine 37-45 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 197-203 10658973-8 2000 By contrast, triggering receptors assemble with homodimers of immune tyrosine-based activation motif (ITAM)-bearing adaptor molecules (i.e., DAP12, CD3 xi) that engage tyrosine kinases (ZAP70 and syk). Tyrosine 69-77 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 186-191 10497187-9 1999 COS cell-expressed glutathione S-transferase-SHP-1L can dephosphorylate tyrosine-phosphorylated ZAP70. Tyrosine 72-80 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 96-101 10576607-0 1999 Age-related impairments in TCR/CD3 activation of ZAP-70 are associated with reduced tyrosine phosphorylations of zeta-chains and p59fyn/p56lck in human T cells. Tyrosine 84-92 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 49-55 10576607-5 1999 Other experiments demonstrated that the age-related impairments of ZAP-70 activation in anti-CD3-stimulated T cells were accompanied by decreased tyrosine phosphorylations of zeta-chains and autophosphorylations of the PTKs p561ck/p59fyn. Tyrosine 146-154 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 67-73 10510363-8 1999 Finally, we show that both Src-homology 2 domains are required for inhibition of invasion, chemotaxis, and aggregation by the truncated ZAP-70, suggesting that ZAP-70 interacts with a phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) sequence. Tyrosine 214-222 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 136-142 10510363-8 1999 Finally, we show that both Src-homology 2 domains are required for inhibition of invasion, chemotaxis, and aggregation by the truncated ZAP-70, suggesting that ZAP-70 interacts with a phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) sequence. Tyrosine 214-222 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 160-166 10583414-2 1999 ZAP-70 enzymatic activation is strictly dependent on the binding, via its SH2 domains, to the triggered TCR and on tyrosine phosphorylation. Tyrosine 115-123 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 10583414-4 1999 We show that deletion of both SH2 domains corresponding to the first 254 residues moderately increases ZAP-70 enzymatic activity on an exogenous substrate in vitro, results in increased tyrosine phosphorylation and produces subtle conformational changes, as judged by altered SDS/PAGE migration. Tyrosine 186-194 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 103-109 10583414-7 1999 We propose that binding of ZAP-70 to the TCR promotes, through conformational changes, its extensive phosphorylation on tyrosine. Tyrosine 120-128 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 27-33 10490604-1 1999 T-cell receptor (TCR) engagement results in the activation of Src family (Lck and Fyn) and ZAP-70 protein tyrosine kinases, leading to tyrosine phosphorylation of multiple cellular substrates including the complex adapter protein c-Cbl. Tyrosine 106-114 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 91-97 10419455-0 1999 T cell activation stimulates the association of enzymatically active tyrosine-phosphorylated ZAP-70 with the Crk adapter proteins. Tyrosine 69-77 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 93-99 10438919-2 1999 Coordinate activation of these pathways is dependent on Lck- and ZAP-70-mediated tyrosine phosphorylation of a 36-kDa linker for activation of T cells and subsequent recruitment of phospholipase C-gamma1, Grb2-SOS, and SLP-76-vav. Tyrosine 81-89 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 65-71 10419455-5 1999 In addition, tyrosine-phosphorylated ZAP-70 co-immunoprecipitated with Crk from a lysate of activated Jurkat cells, and ZAP-70 association with GST-Crk was observed in a lysate of activated human peripheral blood T cells. Tyrosine 13-21 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 37-43 10419455-5 1999 In addition, tyrosine-phosphorylated ZAP-70 co-immunoprecipitated with Crk from a lysate of activated Jurkat cells, and ZAP-70 association with GST-Crk was observed in a lysate of activated human peripheral blood T cells. Tyrosine 13-21 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 120-126 10419455-8 1999 Finally, glutathione S-transferase-Crk fusion proteins were found to interact predominantly with membrane-residing tyrosine-phosphorylated ZAP-70 that exhibited autophosphorylation activity as well as phosphorylation of an exogenous substrate, CFB3. Tyrosine 115-123 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 139-145 10395678-5 1999 Our findings, obtained by using ZAP-70-negative Jurkat T cells, indicate that CD28 costimulation augments TCR-mediated T cell activation by increasing the ZAP-70-mediated Tyr phosphorylation of Vav. Tyrosine 171-174 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 32-38 10395678-5 1999 Our findings, obtained by using ZAP-70-negative Jurkat T cells, indicate that CD28 costimulation augments TCR-mediated T cell activation by increasing the ZAP-70-mediated Tyr phosphorylation of Vav. Tyrosine 171-174 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 155-161 10427998-8 1999 Here, tyrosine phosphorylation of Syk and ZAP-70 was detected after TCR but not after CD28 ligation. Tyrosine 6-14 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 42-48 10427972-6 1999 Cells with the naive phenotype were considerably more active in TCR-dependent tyrosine phosphorylation, both at an overall level and specifically in terms of TCR-zeta and ZAP-70 phosphorylation. Tyrosine 78-86 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 171-177 10201983-6 1999 Analysis of CD3- and CD28-induced signal transduction revealed a deficiency in signaling events that involved repressed tyrosine phosphorylation and enzymatic activities of a family of mitogen-activated protein kinases, extracellular signal-regulated kinase 2, stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK), and p38mapk, as well as p56lck and ZAP-70 in CBTCs compared with those in PBTCs. Tyrosine 120-128 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 364-370 10427998-7 1999 Previous studies implicated the protein tyrosine kinases ZAP-70 and Syk in the TCR-induced tyrosine phosphorylation of LAT. Tyrosine 40-48 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 57-63 10318843-0 1999 Tyrosine 319 in the interdomain B of ZAP-70 is a binding site for the Src homology 2 domain of Lck. Tyrosine 0-8 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 37-43 10202147-2 1999 The interdomain B region of ZAP-70 contains at least three candidate sites of tyrosine phosphorylation. Tyrosine 78-86 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 28-34 10190908-0 1999 ZAP-70 protein promotes tyrosine phosphorylation of T cell receptor signaling motifs (ITAMs) in immature CD4(+)8(+) thymocytes with limiting p56(lck). Tyrosine 24-32 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 10190908-3 1999 We report here that, in DP thymocytes, tyrosine phosphorylation of TCR signaling motifs (ITAMs) by lck, an early event in TCR signal transduction, is dependent upon ZAP-70 protein independent of ZAP-70"s kinase activity. Tyrosine 39-47 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 165-171 10037717-0 1999 Tyrosine 319, a newly identified phosphorylation site of ZAP-70, plays a critical role in T cell antigen receptor signaling. Tyrosine 0-8 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 57-63 10037717-1 1999 Following T cell antigen receptor (TCR) engagement, the protein tyrosine kinase (PTK) ZAP-70 is rapidly phosphorylated on several tyrosine residues, presumably by two mechanisms: an autophosphorylation and a trans-phosphorylation by the Src-family PTK Lck. Tyrosine 64-72 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 86-92 10037717-7 1999 The inhibitory effect of ZAP-70-Y319F correlated with a substantial loss of its activation-induced tyrosine phosphorylation and up-regulation of catalytic activity, as well as with a decreased in vivo capacity to phosphorylate known ZAP-70 substrates, such as SLP-76 and LAT. Tyrosine 99-107 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 25-31 9858619-2 1999 After T-cell receptor stimulation, ZAP-70 associates with the receptor and is phosphorylated on many tyrosines, including Y292, Y315, and Y319 within interdomain B. Tyrosine 101-110 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 35-41 10078535-4 1999 In T cells, Cbl-N binds to the tyrosine-phosphorylated inhibitory site of the protein tyrosine kinase ZAP-70. Tyrosine 31-39 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 102-108 9886389-7 1999 In contrast, SDF-1 treatment resulted in a reduction of tyrosine phosphorylation of the TCR downstream effectors, ZAP-70, SLP-76, and LAT (linker for activation of T cells), suggesting that this chemokine potentially regulates the threshold for T cell activation. Tyrosine 56-64 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 114-120 9858619-8 1999 Biochemically we show that the stimulated tyrosine phosphorylation of Vav, Shc, and ZAP-70 itself is diminished, whereas that of Slp-76 is increased in cells reconstituted with Delta. Tyrosine 42-50 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 84-90 9712039-5 1998 Upon removal of the PTP inhibitor, the tyrosine-phosphorylated proteins, including Lck, Fyn, Syk, Zap70, and CD35 zeta are rapidly dephosphorylated. Tyrosine 39-47 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 98-103 9685404-7 1998 Here, we show that a point mutation (Phe474) of the putative Shc binding site on ZAP-70, spanning tyrosine 474, prevented ZAP-70 interaction with Shc and the subsequent binding of Shc to phospho-zeta. Tyrosine 98-106 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 81-87 9685404-7 1998 Here, we show that a point mutation (Phe474) of the putative Shc binding site on ZAP-70, spanning tyrosine 474, prevented ZAP-70 interaction with Shc and the subsequent binding of Shc to phospho-zeta. Tyrosine 98-106 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 122-128 9685404-0 1998 Tyrosine 474 of ZAP-70 is required for association with the Shc adaptor and for T-cell antigen receptor-dependent gene activation. Tyrosine 0-8 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 16-22 9723676-9 1998 CONCLUSIONS: Our data demonstrate the association of anti-IgE-stimulated, protein-tyrosine phosphorylation by a cascade of tyrosine kinases, including Zap-70 as well as Lyn and Syk, with the initiation of Fc epsilonRI-mediated signaling in human basophils. Tyrosine 82-90 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 151-157 9535874-1 1998 T cell receptor (TCR) triggering induces association of the protein tyrosine kinase ZAP-70, via its two src-homology 2 (SH2) domains, to di-phosphorylated Immunoreceptor Tyrosine-based Activation Motifs (2pY-ITAMs) present in the intracellular tail of the TCR-zeta chain. Tyrosine 170-178 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 84-90 9624129-2 1998 Following receptor engagement, phosphorylation of tyrosine residues within ZAP-70 and Syk is thought to control both kinase activity and recruitment of modulatory factors. Tyrosine 50-58 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 75-81 9624129-3 1998 We report here the characterization of novel mutants of ZAP-70 and Syk, in which conserved C-terminal tyrosine residues have been replaced by phenylalanines (ZAP YF-C, Syk YF-C). Tyrosine 102-110 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 56-62 9553143-7 1998 An in vivo ZAP-70 substrate, SLP-76, implicated in Erk activation, also became rapidly tyrosine-phosphorylated in Jurkat cells, but not in P116 cells, upon treatment with H2O2. Tyrosine 87-95 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 11-17 9723676-6 1998 The tyrosine kinase inhibitor piceatannol spares IgE-mediated Lyn activation but inhibits IgE-induced Syk and Zap-70 activation as well as overall protein tyrosine phosphorylation and secretion. Tyrosine 4-12 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 110-116 9751431-0 1998 Effect of age on mitogen induced protein tyrosine phosphorylation in human T cell and its subsets: down-regulation of tyrosine phosphorylation of ZAP-70. Tyrosine 118-126 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 146-152 9751431-9 1998 Understanding of the biochemical basis of the reduced level of tyrosine phosphorylation of ZAP-70 will be helpful in delineating the molecular basis of age-associated impairment of T cell activation. Tyrosine 63-71 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 91-97 9547330-6 1998 More strikingly, inducible association of ZAP70 to CD3-zeta was strongly inhibited, despite a normal induction of ZAP70 tyrosine phosphorylation. Tyrosine 120-128 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 42-47 9535867-1 1998 Cross-linking of the T cell antigen receptor (TCR)-CD3 complex induces rapid tyrosine phosphorylation and activation of Src (Lck and Fyn) and Syk (Syk and Zap-70) family protein tyrosine kinases (PTKs) which, in turn, phosphorylate multiple intracellular substrates. Tyrosine 77-85 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 155-161 9464824-8 1997 We conclude that p59(fyn) and p56(lck) differently participate in regulating the phosphorylation state of Sam68 in T cells and that ZAP-70 may contribute to Sam68 tyrosine phosphorylation and to the specific recruitment of this molecule after CD3 stimulation. Tyrosine 163-171 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 132-138 9498738-4 1998 Thus, in these cells we observed increased phosphotransferase activity of Lck as well as constitutive tyrosine phosphorylation of the TCR-associated ZAP-70 kinase and expression of the related Syk protein tyrosine kinase. Tyrosine 102-110 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 149-155 9368189-5 1998 Surprisingly, the observed TCR-zeta and ZAP-70 tyrosine phosphorylations appear delayed compared to stimulation via CD3. Tyrosine 47-55 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 40-46 9407100-5 1997 A phosphopeptide predicted by this motif and corresponding to the in vivo negative regulatory phosphorylation site of ZAP-70 (Tyr(P)292) specifically inhibited binding of ZAP-70 to Cbl-N. Tyrosine 126-129 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 118-124 9407100-5 1997 A phosphopeptide predicted by this motif and corresponding to the in vivo negative regulatory phosphorylation site of ZAP-70 (Tyr(P)292) specifically inhibited binding of ZAP-70 to Cbl-N. Tyrosine 126-129 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 171-177 9391116-11 1997 These observations in JAK3 are similar to the findings in the kinase that is closely related to the JAK family, ZAP-70; mutations of tyrosine residues within the putative activation loop of ZAP-70 also have opposing actions. Tyrosine 133-141 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 112-118 9391116-11 1997 These observations in JAK3 are similar to the findings in the kinase that is closely related to the JAK family, ZAP-70; mutations of tyrosine residues within the putative activation loop of ZAP-70 also have opposing actions. Tyrosine 133-141 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 190-196 9371616-5 1997 Second, the ITAM from YE-Nef is phosphorylated on tyrosine residues by Lck and associates with ZAP-70, a T-cell-specific tyrosine kinase. Tyrosine 50-58 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 95-101 9371616-6 1997 The phosphorylation of both conserved tyrosine residues on the ITAM is required for the recruitment of ZAP-70. Tyrosine 38-46 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 103-109 9185620-0 1997 Interaction between the SH2 domains of ZAP-70 and the tyrosine-based activation motif 1 sequence of the zeta subunit of the T-cell receptor. Tyrosine 54-62 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 39-45 9362531-5 1997 Nuclear ZAP-70 becomes tyrosine phosphorylated upon stimulation via the T cell receptor, indicating that it may have an important biologic function. Tyrosine 23-31 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 8-14 9394831-0 1997 Analysis of immunoreceptor tyrosine-based activation motif (ITAM) binding to ZAP-70 by surface plasmon resonance. Tyrosine 27-35 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 77-83 9394831-3 1997 Upon antigen recognition, ITAM become phosphorylated on both tyrosine residues, creating a high affinity binding site for the tandem SH2 domains found in the protein tyrosine kinase ZAP-70. Tyrosine 61-69 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 182-188 9378960-0 1997 In vivo association of CD5 with tyrosine-phosphorylated ZAP-70 and p21 phospho-zeta molecules in human CD3+ thymocytes. Tyrosine 32-40 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 56-62 9378960-7 1997 Although both p21 and p23 tyrosine-phosphorylated forms of zeta as well as phospho-CD3 epsilon molecules were constitutively present in human thymocytes and could be immunoprecipitated with ZAP-70- or CD3 epsilon-specific Abs, the p21 species of zeta was predominant in CD5 immune complexes. Tyrosine 26-34 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 190-196 9378960-8 1997 The interaction between CD5 and ZAP-70 was not observed in CD3-negative thymocytes, where the constitutive tyrosine phosphorylation of ZAP-70 was very low. Tyrosine 107-115 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 32-38 9378960-8 1997 The interaction between CD5 and ZAP-70 was not observed in CD3-negative thymocytes, where the constitutive tyrosine phosphorylation of ZAP-70 was very low. Tyrosine 107-115 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 135-141 9295038-3 1997 Cross-linking of chimeric receptors containing a C-terminal YxxL leucine mutation induces tyrosine phosphorylation of ZAP70 but without stable binding to the phosphorylated ITAM. Tyrosine 90-98 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 118-123 9295038-5 1997 Furthermore, tyrosine phosphorylation of ZAP70 per se is not sufficient to trigger the downstream events leading to IL-2 production. Tyrosine 13-21 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 41-46 9199177-2 1997 ZAP-70 becomes phosphorylated and activated by LCK protein tyrosine kinase after interaction of its two NH2-terminal SH2 domains with tyrosine-phosphorylated subunits of the activated TCR. Tyrosine 59-67 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 9185620-1 1997 One of the key steps involved in T-cell activation is binding of the tyrosine kinase ZAP-70 via its two SH2 domains to peptide segments termed tyrosine-based activation motifs (ITAM) which are present in three of the T-cell receptor (TCR) subunits. Tyrosine 69-77 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 85-91 9120273-2 1997 In this study, we demonstrate that the ZAP70 tyrosine kinase is tyrosine phosphorylated in Jurkat T cells and in purified peripheral T cells after MHC-I ligation. Tyrosine 45-53 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 39-44 9151714-5 1997 Here we demonstrate that a point mutation of tyrosine 315 (Y315F) in ZAP-70, a putative Vav SH2 domain binding site, eliminated the Vav- ZAP-70 interaction. Tyrosine 45-53 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 69-75 9151714-5 1997 Here we demonstrate that a point mutation of tyrosine 315 (Y315F) in ZAP-70, a putative Vav SH2 domain binding site, eliminated the Vav- ZAP-70 interaction. Tyrosine 45-53 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 137-143 9151714-7 1997 Surprisingly, this mutation also resulted in marked reduction in the tyrosine phosphorylation of ZAP-70, Vav, SLP-76, and Shc. Tyrosine 69-77 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 97-103 9120273-3 1997 The tyrosine-phosphorylated ZAP70 kinase exhibits a particular phenotype with low affinities for proteins at 21, 40, 60, and 120 kDa, proteins normally co-precipitated with ZAP70 after TCR/CD3 stimulation. Tyrosine 4-12 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 28-33 9120273-3 1997 The tyrosine-phosphorylated ZAP70 kinase exhibits a particular phenotype with low affinities for proteins at 21, 40, 60, and 120 kDa, proteins normally co-precipitated with ZAP70 after TCR/CD3 stimulation. Tyrosine 4-12 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 173-178 8955094-0 1996 Mutation of tyrosines 492/493 in the kinase domain of ZAP-70 affects multiple T-cell receptor signaling pathways. Tyrosine 12-21 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 54-60 9079813-4 1997 Results demonstrate that in BW5147 wild-type TCR, tail-less zeta TCR, CD3epsilon, and TCRzeta transduce signals leading to tyrosine phosphorylation of similar sets of cellular substrates, including the receptor subunits, Fyn, ZAP-70, and phospholipase Cgamma1 (PLCgamma1). Tyrosine 123-131 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 226-232 9036949-3 1997 We show MHC class II-restricted antagonist activity was associated with a differential pattern of early tyrosine phosphorylation events that was characterized by a preponderance of phosphorylation of low molecular mass TCRzeta and the failure to phosphorylate Zap-70. Tyrosine 104-112 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 260-266 9029101-2 1997 Current models propose that Src family kinases are critical in immune response signal transduction through their role in phosphorylation of tyrosine residues within immunoreceptor tyrosine activation motifs (ITAMs; which recruit the SH2 domains of Syk or ZAP-70) and by direct phosphorylation of Syk and ZAP-70. Tyrosine 140-148 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 255-261 9029101-2 1997 Current models propose that Src family kinases are critical in immune response signal transduction through their role in phosphorylation of tyrosine residues within immunoreceptor tyrosine activation motifs (ITAMs; which recruit the SH2 domains of Syk or ZAP-70) and by direct phosphorylation of Syk and ZAP-70. Tyrosine 140-148 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 304-310 9029101-2 1997 Current models propose that Src family kinases are critical in immune response signal transduction through their role in phosphorylation of tyrosine residues within immunoreceptor tyrosine activation motifs (ITAMs; which recruit the SH2 domains of Syk or ZAP-70) and by direct phosphorylation of Syk and ZAP-70. Tyrosine 180-188 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 255-261 9029101-2 1997 Current models propose that Src family kinases are critical in immune response signal transduction through their role in phosphorylation of tyrosine residues within immunoreceptor tyrosine activation motifs (ITAMs; which recruit the SH2 domains of Syk or ZAP-70) and by direct phosphorylation of Syk and ZAP-70. Tyrosine 180-188 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 304-310 8955094-3 1996 We overexpressed in the Jurkat T-cell line ZAP-70 mutated on Tyr-492 and Tyr-493 in the putative regulatory loop of its kinase domain. Tyrosine 61-64 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 43-49 8955094-3 1996 We overexpressed in the Jurkat T-cell line ZAP-70 mutated on Tyr-492 and Tyr-493 in the putative regulatory loop of its kinase domain. Tyrosine 73-76 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 43-49 8955094-7 1996 The ZAP-70 mutant studied here could be phosphorylated on tyrosine when associated to the TCR zeta chain and was able to bind p56(lck). Tyrosine 58-66 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 4-10 8955094-9 1996 Our data are most consistent with a model in which recruitment to the TCR allows ZAP-70 autophosphorylation and binding to p56(lck), which in turn phosphorylates Tyr-492 and/or Tyr-493 with consequent up-regulation of the ZAP-70 kinase activity. Tyrosine 162-165 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 81-87 8955094-9 1996 Our data are most consistent with a model in which recruitment to the TCR allows ZAP-70 autophosphorylation and binding to p56(lck), which in turn phosphorylates Tyr-492 and/or Tyr-493 with consequent up-regulation of the ZAP-70 kinase activity. Tyrosine 162-165 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 222-228 8955094-9 1996 Our data are most consistent with a model in which recruitment to the TCR allows ZAP-70 autophosphorylation and binding to p56(lck), which in turn phosphorylates Tyr-492 and/or Tyr-493 with consequent up-regulation of the ZAP-70 kinase activity. Tyrosine 177-180 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 81-87 8906806-2 1996 The T cell-specific protein tyrosine kinase (PTK) ZAP-70 is believed to play a key role in early tyrosine phosphorylations of cellular proteins induced by CD3 stimulation. Tyrosine 28-36 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 50-56 8943371-2 1996 When its two tyrosines are phosphorylated, ITAM forms a binding site for ZAP-70, one of the cytoplasmic protein tyrosine kinases essential for T-cell activation. Tyrosine 13-22 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 73-79 8906806-5 1996 Several studies have suggested a model in which p56lck would be responsible after CD3 triggering for the phosphorylation of particular tyrosine residues in the immunoreceptor tyrosine-based activation motifs of the CD3 chains, inducing the recruitment and the tyrosine phosphorylation of ZAP-70. Tyrosine 135-143 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 288-294 8906806-3 1996 We show in the present report that ZAP-70 is insignificantly tyrosine phosphorylated and recruited to CD3 after CD2 stimulation in Jurkat T cells. Tyrosine 61-69 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 35-41 8906806-5 1996 Several studies have suggested a model in which p56lck would be responsible after CD3 triggering for the phosphorylation of particular tyrosine residues in the immunoreceptor tyrosine-based activation motifs of the CD3 chains, inducing the recruitment and the tyrosine phosphorylation of ZAP-70. Tyrosine 175-183 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 288-294 8906806-5 1996 Several studies have suggested a model in which p56lck would be responsible after CD3 triggering for the phosphorylation of particular tyrosine residues in the immunoreceptor tyrosine-based activation motifs of the CD3 chains, inducing the recruitment and the tyrosine phosphorylation of ZAP-70. Tyrosine 175-183 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 288-294 8816383-6 1996 In contrast, CD94 ligation on group B clones had none of the above noted effects and instead inhibited the FcR-induced tyrosine phosphorylations of ZAP-70 and phospholipase C-gamma 2, the formation of phospho-zeta/ZAP-70 complexes, and the release of inositol phosphates. Tyrosine 119-127 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 148-154 8901551-2 1996 During T-cell activation, Zap-70 becomes associated via its src homology type 2 (SH2) domains with tyrosine-phosphorylated immune-receptor tyrosine activating motif (ITAM) sequences in the cytoplasmic zeta chain of the T-cell receptor. Tyrosine 99-107 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 26-32 8901551-2 1996 During T-cell activation, Zap-70 becomes associated via its src homology type 2 (SH2) domains with tyrosine-phosphorylated immune-receptor tyrosine activating motif (ITAM) sequences in the cytoplasmic zeta chain of the T-cell receptor. Tyrosine 139-147 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 26-32 8920891-7 1996 After transduction, ZAP-70 was detected at levels equivalent to those observed in normal cells, and was appropriately phosphorylated on tyrosine after receptor engagement. Tyrosine 136-144 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 20-26 8845015-6 1996 Using this method we found that both ZAP-70 and p72syk bound tyrosine phosphorylated TCR zeta very efficiently. Tyrosine 61-69 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 37-43 8814252-3 1996 We have previously shown that the interaction of the p56lck SH2 domain with zeta-associated, tyrosine phosphorylated ZAP-70 and Syk kinases leads to an enhanced association of CD4 with TCR/CD3/zeta complex after CD3 stimulation of Jurkat cells. Tyrosine 93-101 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 117-123 8814252-6 1996 A phosphopeptide competing in vitro for the binding of tyrosine phosphorylated proteins to the SH2 domain of p56lck specifically impedes the association of ZAP-70 with CD8 alpha alpha/p56lck without affecting the zeta/ZAP-70 interaction. Tyrosine 55-63 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 156-162 8814252-6 1996 A phosphopeptide competing in vitro for the binding of tyrosine phosphorylated proteins to the SH2 domain of p56lck specifically impedes the association of ZAP-70 with CD8 alpha alpha/p56lck without affecting the zeta/ZAP-70 interaction. Tyrosine 55-63 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 218-224 8760790-4 1996 In contrast, TCR ligation in the presence of B7 costimulation, which results in productive immunity, activates tyrosine phosphorylation of TCR zeta and CD3 chains, which associate with activated lck and zeta-associated protein (ZAP) 70. Tyrosine 111-119 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 203-235 8551236-3 1996 We have attempted to identify a 120-kD tyrosine-phosphorylated protein (p120) that associates with Zap-70 in activated T lymphocytes. Tyrosine 39-47 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 99-105 8663155-6 1996 The activity of the recombinant ZAP-70, unlike that of the homologous protein tyrosine kinase, Syk, was not affected by binding of TCR-derived tyrosine phosphorylated immunoreceptor tyrosine-based activation motif peptides. Tyrosine 78-86 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 32-38 8657120-1 1996 A critical event in signaling in immune cells is the interaction of Syk or ZAP-70 protein tyrosine kinases with multisubunit receptors that contain an approximately 18-amino-acid domain called the immunoreceptor tyrosine-based activation motif (ITAM). Tyrosine 90-98 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 75-81 8627172-1 1996 Zeta-associated protein (ZAP)-70 is a cytoplasmic protein tyrosine required for T cell antigen receptor (TCR) signaling and development. Tyrosine 58-66 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-32 8627172-3 1996 ZAP-70 interacts with the TCR by binding to tyrosine-phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) present in the invariant subunits of the TCR complex. Tyrosine 44-52 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 8627172-3 1996 ZAP-70 interacts with the TCR by binding to tyrosine-phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) present in the invariant subunits of the TCR complex. Tyrosine 83-91 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 8576267-5 1996 We show that ligation of CD44 by monoclonal antibodies (mAbs) transduces signals to T cells which lead to tyrosine phosphorylation of ZAP-70 and other intracellular proteins. Tyrosine 106-114 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 134-140 8551236-7 1996 Finally, using a heterologous system, it was demonstrated that the ability of Zap-70 to cause tyrosine phosphorylation of p120c-cbl was dependent on Lck- or FynT-mediated signals. Tyrosine 94-102 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 78-84 7594516-5 1995 The altered tyrosine phosphorylation in anergic T cells may be caused by a defect in tyrosine phosphorylation of TCR zeta-chain and its subsequent association with ZAP-70 tyrosine kinase. Tyrosine 12-20 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 164-170 8530437-3 1995 The ZAP-70 associated with tubulin was preferentially tyrosine-phosphorylated after T cell antigen receptor stimulation of Jurkat T cells, suggesting that this interaction was functionally significant. Tyrosine 54-62 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 4-10 7594516-5 1995 The altered tyrosine phosphorylation in anergic T cells may be caused by a defect in tyrosine phosphorylation of TCR zeta-chain and its subsequent association with ZAP-70 tyrosine kinase. Tyrosine 85-93 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 164-170 8525473-4 1995 Antibody mediated co-ligation of the T-cell antigen receptor (TCR/CD3) with class II molecules resulted in augmented tyrosine phosphorylation of ZAP-70. Tyrosine 117-125 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 145-151 8613493-4 1995 Peripheral CD4+ T cells from the zap-70(-1-1) patients exhibit markedly reduced tyrosine phosphorylation, fail to produce interleukin-2, and do not proliferate in response to T-cell receptor stimulation by mitogens or antigens. Tyrosine 80-88 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 33-39 7589084-2 1995 In the present study, we explored the role of phosphorylation of the two ITAM tyrosine residues in the interactions of the motif with the PTK ZAP-70 and p59fyn. Tyrosine 78-86 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 142-148 7589084-3 1995 The data show that the phosphorylation of a single tyrosine within the motif enables binding of p59fyn, whereas phosphorylation of both tyrosines within the motif is required for maximal binding of the PTK ZAP-70. Tyrosine 136-145 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 206-212 8525473-5 1995 Comparable to antibody induced receptor ligation, bacterial superantigen (SEA and SEB) treatment of HLA-DR+ T-cells stimulated ZAP-70 tyrosine phosphorylation, consistent with class II transmembrane signaling by ligation of HLA-DR and V beta in cis. Tyrosine 134-142 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 127-133 8525473-6 1995 Modulation of the TCR/CD3 led to abrogation of class II induced ZAP-70 tyrosine phosphorylation, but did not result in sequestering of ZAP-70 from the cellular cytoplasm. Tyrosine 71-79 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 64-70 7539794-0 1995 A comparison of the interaction of Shc and the tyrosine kinase ZAP-70 with the T cell antigen receptor zeta chain tyrosine-based activation motif. Tyrosine 47-55 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 63-69 7642520-0 1995 Activating and inhibitory mutations in adjacent tyrosines in the kinase domain of ZAP-70. Tyrosine 48-57 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 82-88 7642520-2 1995 The strong correlation between tyrosine phosphorylation of ZAP-70 and its acquisition of increased kinase activity suggests that is is positively regulated by tyrosine phosphorylation. Tyrosine 31-39 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 59-65 7642520-2 1995 The strong correlation between tyrosine phosphorylation of ZAP-70 and its acquisition of increased kinase activity suggests that is is positively regulated by tyrosine phosphorylation. Tyrosine 159-167 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 59-65 7642520-3 1995 Previously, we identified tyrosines 492 and 493 of ZAP-70 as being sites of in vivo phosphorylation in response to T cell receptor engagement. Tyrosine 26-35 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 51-57 7642520-6 1995 This suggests that Tyr-493 phosphorylation is required for the tyrosine phosphorylation-induced activation of ZAP-70. Tyrosine 19-22 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 110-116 7642520-6 1995 This suggests that Tyr-493 phosphorylation is required for the tyrosine phosphorylation-induced activation of ZAP-70. Tyrosine 63-71 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 110-116 7642520-8 1995 These results reveal that critical tyrosine residues in the kinase domain of ZAP-70 are important in regulation of its catalytic activity. Tyrosine 35-43 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 77-83 7539794-2 1995 The present study shows that phosphorylation of both tyrosines within the motif is required for high affinity binding of the tyrosine kinase ZAP-70 whereas phosphorylation of the single COOH-terminal tyrosine within the motif is optimal for the binding of the adapter Shc. Tyrosine 53-62 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 141-147 7539794-2 1995 The present study shows that phosphorylation of both tyrosines within the motif is required for high affinity binding of the tyrosine kinase ZAP-70 whereas phosphorylation of the single COOH-terminal tyrosine within the motif is optimal for the binding of the adapter Shc. Tyrosine 53-61 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 141-147 7528772-0 1995 ZAP-70 binding specificity to T cell receptor tyrosine-based activation motifs: the tandem SH2 domains of ZAP-70 bind distinct tyrosine-based activation motifs with varying affinity. Tyrosine 46-54 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 7781602-0 1995 Activation of ZAP-70 kinase activity by phosphorylation of tyrosine 493 is required for lymphocyte antigen receptor function. Tyrosine 59-67 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 14-20 7781602-2 1995 ZAP-70 is associated with the phosphorylated antigen receptor and undergoes tyrosine phosphorylation following receptor activation. Tyrosine 76-84 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 7781602-3 1995 We demonstrate here that tyrosine phosphorylation of ZAP-70 results in an increase in its catalytic activity and that this activation is mediated by the phosphorylation of tyrosine residue 493 by the src family of PTKs. Tyrosine 25-33 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 53-59 7781602-3 1995 We demonstrate here that tyrosine phosphorylation of ZAP-70 results in an increase in its catalytic activity and that this activation is mediated by the phosphorylation of tyrosine residue 493 by the src family of PTKs. Tyrosine 172-180 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 53-59 7761456-1 1995 Tyrosine phosphorylation of a 17-amino acid immunoreceptor tyrosine-based activation motif (ITAM), conserved in each of the signaling subunits of the T-cell antigen receptor (TCR), mediates the recruitment of ZAP-70 and syk protein-tyrosine kinases (PTKs) to the activated receptor. Tyrosine 0-8 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 209-215 7761456-1 1995 Tyrosine phosphorylation of a 17-amino acid immunoreceptor tyrosine-based activation motif (ITAM), conserved in each of the signaling subunits of the T-cell antigen receptor (TCR), mediates the recruitment of ZAP-70 and syk protein-tyrosine kinases (PTKs) to the activated receptor. Tyrosine 59-67 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 209-215 7852351-2 1995 By analyzing derivatives containing an activated version of either p56lck or p59fynT, it was observed that the two Src-related enzymes augmented T-cell receptor (TCR)-mediated tyrosine phosphorylation of Zap-70, as well as its association with components of the antigen receptor complex. Tyrosine 176-184 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 204-210 7852351-3 1995 Importantly, the accumulation of TCR.Zap-70 complexes quantitatively and temporally correlated with the induction of tyrosine phosphorylation of the CD3 and zeta chains of TCR. Tyrosine 117-125 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 37-43 7852351-4 1995 Using a CD4-positive variant of BI-141, we also found that the ability of Zap-70 to undergo tyrosine phosphorylation and associate with TCR was enhanced by aggregation of TCR with the CD4 co-receptor. Tyrosine 92-100 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 74-80 7852351-5 1995 Further studies allowed the identification of two distinct pools of tyrosine-phosphorylated Zap-70 in activated T-cells. Tyrosine 68-76 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 92-98 7749439-4 1995 Peripheral CD4+ T cells from the zap-70-/- exhibit markedly reduced tyrosine phosphorylation, fail to produce IL-2, and do not proliferate in response to TCR stimulation by mitogens or antigens. Tyrosine 68-76 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 33-39 7539035-4 1995 We have previously shown that the p56lck SH2 domain binds directly to tyrosine-phosphorylated ZAP-70. Tyrosine 70-78 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 94-100 7539035-6 1995 A tyrosine-phosphorylated peptide containing the sequence predicted to be optimal for binding to the SH2 domain of src family kinases specifically competes for this association, indicating that tyrosine-phosphorylated ZAP-70 and Syk bind to p56lck by an SH2-mediated interaction. Tyrosine 2-10 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 218-224 7539035-6 1995 A tyrosine-phosphorylated peptide containing the sequence predicted to be optimal for binding to the SH2 domain of src family kinases specifically competes for this association, indicating that tyrosine-phosphorylated ZAP-70 and Syk bind to p56lck by an SH2-mediated interaction. Tyrosine 194-202 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 218-224 7539035-9 1995 We propose that the interaction of the p56lck SH2 domain with zeta-associated tyrosine-phosphorylated ZAP-70 and/or Syk enables CD4 to associate with antigen-stimulated TCR/CD3/zeta complexes. Tyrosine 78-86 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 102-108 7760813-2 1995 During T-cell activation, ZAP-70 binds to a conserved signalling motif known as the immune receptor tyrosine activating motif (ITAM) and becomes tyrosine phosphorylated. Tyrosine 100-108 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 26-32 7760813-2 1995 During T-cell activation, ZAP-70 binds to a conserved signalling motif known as the immune receptor tyrosine activating motif (ITAM) and becomes tyrosine phosphorylated. Tyrosine 145-153 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 26-32 7760813-4 1995 The ability of ZAP-70 to phosphorylate itself, but not exogenous substrates, was enhanced when it was bound to the tyrosine-phosphorylated TCR zeta and eta chains or to a construct that contained duplicated epsilon ITAMs. Tyrosine 115-123 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 15-21 7760813-6 1995 In addition, autophosphorylation of ZAP-70 when bound to zeta or eta resulted in the generation of multiple distinct ZAP-70 phosphorylated tyrosine residues which had the capacity to bind the SH2 domains of fyn, lck, GAP, and abl. Tyrosine 139-147 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 36-42 7760813-6 1995 In addition, autophosphorylation of ZAP-70 when bound to zeta or eta resulted in the generation of multiple distinct ZAP-70 phosphorylated tyrosine residues which had the capacity to bind the SH2 domains of fyn, lck, GAP, and abl. Tyrosine 139-147 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 117-123 7760813-8 1995 Tyrosine-phosphorylated ZAP-70 then mediates downstream signalling by recruiting SH2 domain-containing signalling proteins. Tyrosine 0-8 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 24-30 7822334-2 1995 TAMs become tyrosine-phosphorylated upon TCR stimulation, creating a high affinity binding site for the tandem SH2 domains of ZAP-70. Tyrosine 12-20 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 126-132 7822334-4 1995 Inhibition of this association prevented TCR-stimulated tyrosine phosphorylation of ZAP-70 and reduced ZAP-70 kinase activity to basal levels. Tyrosine 56-64 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 84-90 7822334-4 1995 Inhibition of this association prevented TCR-stimulated tyrosine phosphorylation of ZAP-70 and reduced ZAP-70 kinase activity to basal levels. Tyrosine 56-64 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 103-109 7822334-5 1995 The reduction in ZAP-70 activity coincided with reduced tyrosine phosphorylation of a number of substrates. Tyrosine 56-64 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 17-23 7528772-0 1995 ZAP-70 binding specificity to T cell receptor tyrosine-based activation motifs: the tandem SH2 domains of ZAP-70 bind distinct tyrosine-based activation motifs with varying affinity. Tyrosine 46-54 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 106-112 7528772-0 1995 ZAP-70 binding specificity to T cell receptor tyrosine-based activation motifs: the tandem SH2 domains of ZAP-70 bind distinct tyrosine-based activation motifs with varying affinity. Tyrosine 127-135 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 0-6 7528772-0 1995 ZAP-70 binding specificity to T cell receptor tyrosine-based activation motifs: the tandem SH2 domains of ZAP-70 bind distinct tyrosine-based activation motifs with varying affinity. Tyrosine 127-135 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 106-112 7528772-4 1995 Tyrosine-phosphorylated TAMs serve as targets for binding of the zeta-associated protein (ZAP-70) tyrosine kinase via its tandem SH2 domains. Tyrosine 0-8 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 90-96 7528772-10 1995 Similar studies demonstrated that the ZAP-70 tandem SH2 domain can bind a TCR zeta 3 TAM peptide in which both tyrosine residues are phosphorylated: Little or no binding was observed with peptides phosphorylated at only one tyrosine residue, or a nonphosphorylated peptide. Tyrosine 111-119 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 38-44 7528772-10 1995 Similar studies demonstrated that the ZAP-70 tandem SH2 domain can bind a TCR zeta 3 TAM peptide in which both tyrosine residues are phosphorylated: Little or no binding was observed with peptides phosphorylated at only one tyrosine residue, or a nonphosphorylated peptide. Tyrosine 224-232 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 38-44 7528772-12 1995 All four doubly tyrosine phosphorylated TAM peptides cross-compete with each other for binding to the tandem SH2 domains of ZAP-70. Tyrosine 16-24 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 124-130 7528772-14 1995 The results provide further evidence that the ZAP-70 interaction with the TCR requires prior phosphorylation of both tyrosine residues within a TAM motif. Tyrosine 117-125 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 46-52 7961936-0 1994 Identification by electrospray ionization mass spectrometry of the sites of tyrosine phosphorylation induced in activated Jurkat T cells on the protein tyrosine kinase ZAP-70. Tyrosine 76-84 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 168-174 7989747-9 1994 More importantly, CD27 ligation induced protein tyrosine phosphorylation, especially 70 kDa of cellular substrate, including ZAP-70, in T cells. Tyrosine 48-56 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 125-131 7961936-3 1994 We applied this technique to the analysis of in vitro sites of tyrosine phosphorylation induced on the T cell-specific protein tyrosine kinase ZAP-70 in the absence and presence of p56lck. Tyrosine 63-71 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 143-149 7961936-4 1994 We show that ZAP-70 has a primary autophosphorylation site at Tyr-292, with a secondary site at Tyr-126. Tyrosine 62-65 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 13-19 7961936-4 1994 We show that ZAP-70 has a primary autophosphorylation site at Tyr-292, with a secondary site at Tyr-126. Tyrosine 96-99 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 13-19 7961936-6 1994 By comparative two-dimensional phosphopeptide mapping, we show that ZAP-70 isolated from Jurkat T cells also autophosphorylates at Tyr-292 and Tyr-126. Tyrosine 131-134 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 68-74 7961936-6 1994 By comparative two-dimensional phosphopeptide mapping, we show that ZAP-70 isolated from Jurkat T cells also autophosphorylates at Tyr-292 and Tyr-126. Tyrosine 143-146 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 68-74 7937868-2 1994 Crosslinking Fc gamma RIIA with anti-Fc gamma RII monoclonal antibody also induced tyrosine phosphorylation of multiple proteins including Fc gamma RIIA, ZAP-70, p72SYK, and phospholipase C gamma 1 subunit and an increase in intracellular Ca2+ concentration. Tyrosine 83-91 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 154-160 7517560-3 1994 Subsequently, the chimera becomes associated with several tyrosine-phosphorylated proteins, among them the 70-kDa protein tyrosine kinase ZAP70. Tyrosine 58-66 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 138-143 7819147-8 1994 Together, these results demonstrate that: (i) PTKs bound to CD16 mediate signal transduction, (ii) ZAP-70 plays a crucial role in signaling and (iii) apart from tyrosine residues in the activation motif, other structural constraints also regulate the interaction of PTKs with the receptor molecule. Tyrosine 161-169 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 99-105 7517560-5 1994 Recombinant protein containing the two tandem SH2 domains derived from ZAP70 binds to a synthetic peptide corresponding to the above 18-amino acid motif but only when both tyrosines are phosphorylated; in contrast, little or no binding is observed to monophosphorylated or nonphosphorylated analogues. Tyrosine 172-181 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 71-76 8196616-4 1994 Here we demonstrate that the tyrosine-based activation motif is required and sufficient for association with the tyrosine kinases p59fyn and ZAP-70, suggesting that association with these kinases is a general feature of this motif. Tyrosine 29-37 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 141-147 8196616-11 1994 Interestingly, the interaction of ZAP-70 with the motif was dependent on the presence of both ZAP-70 SH2 domains and both of the tyrosine residues in the motif, suggesting that ZAP-70 interacts with two phosphotyrosine residues and that the binding of the two SH2 domains is cooperative. Tyrosine 129-137 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 34-40 8196616-11 1994 Interestingly, the interaction of ZAP-70 with the motif was dependent on the presence of both ZAP-70 SH2 domains and both of the tyrosine residues in the motif, suggesting that ZAP-70 interacts with two phosphotyrosine residues and that the binding of the two SH2 domains is cooperative. Tyrosine 129-137 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 94-100 8196616-9 1994 The spacing between the tyrosines was also important, as deletion of two residues disrupted binding of ZAP-70, although p59fyn binding was not disrupted. Tyrosine 24-33 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 103-109 8196616-11 1994 Interestingly, the interaction of ZAP-70 with the motif was dependent on the presence of both ZAP-70 SH2 domains and both of the tyrosine residues in the motif, suggesting that ZAP-70 interacts with two phosphotyrosine residues and that the binding of the two SH2 domains is cooperative. Tyrosine 129-137 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 94-100 8196616-13 1994 We propose that the activation of cells by the tyrosine activating motif occurs in four discrete steps: binding of p59fyn, phosphorylation of the motif, binding of ZAP-70, and activation of ZAP-70 kinase activity. Tyrosine 47-55 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 164-170 8196616-10 1994 Most of the defined features of the tyrosine activation motif are therefore requirements for ZAP-70 binding. Tyrosine 36-44 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 93-99 8196616-13 1994 We propose that the activation of cells by the tyrosine activating motif occurs in four discrete steps: binding of p59fyn, phosphorylation of the motif, binding of ZAP-70, and activation of ZAP-70 kinase activity. Tyrosine 47-55 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 190-196 8193541-3 1994 Further, receptor ligation induces tyrosine phosphorylation of this motif, and this initiates SH2-mediated association and activation of Src-family kinases and, apparently, ZAP70 kinases. Tyrosine 35-43 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 173-178 8124727-4 1994 Peripheral CD4+ T cells from the zap-70-/- patients exhibit markedly reduced tyrosine phosphorylation, fail to produce interleukin-2, and do not proliferate in response to T cell receptor stimulation by mitogens or antigens. Tyrosine 77-85 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 33-39 8120446-7 1994 A decrease in the activity of src-related kinases was caused primarily by their lower expression, whereas expression of ZAP-70 was unchanged but its response to CD3 cross-linking was diminished, correlating with the deficient tyrosine phosphorylation of the CD3 zeta-chain, recently observed in J32-3.2. Tyrosine 226-234 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 120-126 8289790-8 1994 Cytoplasmic tyrosine residues in Ig beta were required for recruitment and activation of ZAP-70, but these amino acids were not essential for the activation of Fyn and Lck. Tyrosine 12-20 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 89-95 7693848-0 1993 The CD3 chains of the T cell antigen receptor associate with the ZAP-70 tyrosine kinase and are tyrosine phosphorylated after receptor stimulation. Tyrosine 72-80 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 65-71 34960785-3 2021 Here we show that expression of the C protein induced specific tyrosine phosphorylation of the TCR-related signaling proteins ZAP-70, LAT and PLC-gamma in the T cells. Tyrosine 63-71 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 126-132 8366117-3 1993 Here we report that the tandem SH2 domains of ZAP-70, expressed as a fusion protein, bind to tyrosine-phosphorylated CD3 epsilon and TCR zeta from activated Jurkat T cell lysates. Tyrosine 93-101 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 46-52 8344348-4 1993 Here we show that CD16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16: zeta: gamma receptor complex, results in the tyrosine phosphorylation of a 70 kDa zeta-associated protein (pp70). Tyrosine 179-187 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 209-239 1423621-4 1992 We have recently identified a 70 kd tyrosine phosphoprotein (ZAP-70) that associates with zeta and undergoes tyrosine phosphorylation following TCR stimulation. Tyrosine 36-44 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 61-67 1423621-7 1992 Moreover, tyrosine phosphorylation and association of ZAP-70 with zeta require the presence of src family PTKs and provide a potential mechanism by which the src family PTKs and ZAP-70 may interact to mediate TCR signal transduction. Tyrosine 10-18 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 178-184 34413312-4 2021 The ZAP70 biosensor elucidates the role of immunoreceptor tyrosine-based activation motif (ITAM) in affecting ZAP70 activation to regulate CAR functions. Tyrosine 58-66 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 4-9 34413312-4 2021 The ZAP70 biosensor elucidates the role of immunoreceptor tyrosine-based activation motif (ITAM) in affecting ZAP70 activation to regulate CAR functions. Tyrosine 58-66 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 110-115 34414199-7 2021 Herein, we report our findings, demonstrating the immune reactivating effect of C24D via the phosphorylation of the tyrosine 505 and 394 in Lck, the tyrosine 493 in ZAP-70 and the tyrosine 172 in VAV-1 proteins in the CD45 signaling pathway. Tyrosine 149-157 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 165-171 34394081-10 2021 Further, immunoprecipitation assays show that TCR triggering induces tyrosine phosphorylation of Zip6, which has at least three putative tyrosine motifs in its long cytoplasmic region, and this phosphorylation is coupled with its physical interaction with Zap70. Tyrosine 69-77 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 256-261