LAT The ZAP-70 Tyrosine Kinase Substrate that Links T Cell Receptor to Cellular Activation

@article{Zhang1998LATTZ,
  title={LAT The ZAP-70 Tyrosine Kinase Substrate that Links T Cell Receptor to Cellular Activation},
  author={Weiguo Zhang and Joanne Sloan-Lancaster and Jason Kitchen and Ronald P. Trible and Lawrence E. Samelson},
  journal={Cell},
  year={1998},
  volume={92},
  pages={83-92}
}
Despite extensive study, several of the major components involved in T cell receptor-mediated signaling remain unidentified. Here we report the cloning of the cDNA for a highly tyrosine-phosphorylated 36-38 kDa protein, previously characterized by its association with Grb2, phospholipase C-gamma1, and the p85 subunit of phosphoinositide 3-kinase. Deduced amino acid sequence identifies a novel integral membrane protein containing multiple potential tyrosine phosphorylation sites. We show that… Expand
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Differential T-Cell Antigen Receptor Signaling Mediated by the Src Family Kinases Lck and Fyn
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Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76.
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Inhibition of T Cell Signaling by Mitogen-activated Protein Kinase-targeted Hematopoietic Tyrosine Phosphatase (HePTP)*
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Structural Basis for Activation of ZAP-70 by Phosphorylation of the SH2-Kinase Linker
  • Qingrong Yan, T. Barros, +4 authors J. Kuriyan
  • Medicine, Biology
  • Molecular and Cellular Biology
  • 2013
TLDR
A revised model 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, identifies distinct roles for these two tyrosines. Expand
The Structural Basis for Activation and Inhibition of ZAP-70 Kinase Domain
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The present study investigates molecular mechanisms of activation and inhibition of ZAP–70 via atomically detailed molecular dynamics simulation approaches, and reveals a novel, potentially druggable pocket in close proximity to the activation loop of the kinase, which offers promise in future design of specific kinase inhibitors. Expand
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References

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Activating and Inhibitory Mutations in Adjacent Tyrosines in the Kinase Domain of ZAP-70 (*)
TLDR
Results reveal that critical tyrosine residues in the kinase domain of ZAP-70 are important in regulation of its catalytic activity, and that Tyr-493 phosphorylation is required for the tyrosines phosphorylated in response to T cell receptor engagement. Expand
Phosphorylation of SLP-76 by the ZAP-70 Protein-tyrosine Kinase Is Required for T-cell Receptor Function*
TLDR
Evidence is presented herein that phosphorylation of SLP-76 by ZAP-70 provides an important functional link between the T-cell receptor and activation of ras and calcium pathways. Expand
T Cell Activation-dependent Association between the p85 Subunit of the Phosphatidylinositol 3-Kinase and Grb2/Phospholipase C-γ1-binding Phosphotyrosyl Protein pp36/38 (*)
TLDR
The role of pp36/38 is strongly suggested in recruiting PI-3-K to the cell membrane and further support the idea that pp36 /38 is a multifunctional docking protein for SH2 domain-containing signaling proteins in T cells. Expand
Characterization of Lnk
TLDR
It is reported that although Lnk becomes phosphorylated during T cell activation, it plays no limiting role in the TCR signaling process, and together these studies suggest that LnK participates in signaling from receptors other than antigen receptors in lymphocytes. Expand
The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the T cell antigen receptor.
TLDR
It is shown that the 120-kDa protein tyrosine phosphorylated in Jurkat T cells upon TCR engagement is p120cbl, the product of the cellular homolog of a transforming oncogene that can interact with several known signaling molecules. Expand
Lymphocyte lineage-restricted tyrosine-phosphorylated proteins that bind PLC gamma 1 SH2 domains.
TLDR
A fusion protein containing the SH2 domains of human PLC gamma 1 and human IgG1 heavy chain constant region is generated to identify lymphocyte phosphoprotein-binding PL gamma 1 SH2domain following cellular activation, suggesting that lymphocyte PLC Gamma 1 SH1-binding proteins are cell lineage specific and may be transiently associated with activated PLCGamma 1. Expand
Cloning and characterization of Lnk, a signal transduction protein that links T-cell receptor activation signal to phospholipase C gamma 1, Grb2, and phosphatidylinositol 3-kinase.
TLDR
The results suggest that Lnk becomes tyrosine phosphorylated and links the immediate tyrosin phosphorylation signals of the TCR to the distal phosphatidylinositol 3-kinase, phospholipase C gamma 1 and Ras signaling pathways through its multifunctional tyrosining site. Expand
GRB2 and phospholipase C-gamma 1 associate with a 36- to 38-kilodalton phosphotyrosine protein after T-cell receptor stimulation.
TLDR
It is suggested that pp36-38 may be a bridging protein, coupling different signalling molecules to cytoplasmic PTKs regulated by the TCR, and low levels of PLC-gamma 1 are detected in GRB2 immunoprecipitates in support of this notion. Expand
Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production
TLDR
In vitro experiments show that the SH2 domain of SLP-76 associates with the 62- and 130-kD proteins and additionally with a serine/threonine kinase, and in vivo associations of SLp-76 with several proteins that potentially participate in T cell activation and implicate the protein itself as an important molecule in TCR-mediated IL-2 production are documented. Expand
Activation of ZAP‐70 kinase activity by phosphorylation of tyrosine 493 is required for lymphocyte antigen receptor function.
TLDR
It is demonstrated that phosphorylation of Y493 and activation of ZAP‐70 is required for antigen receptor‐mediated induction of interleukin‐2 (IL‐2) secretion in lymphocytes and that this activation is mediated by the phosphorylated tyrosine residue 493 by the src family of PTKs. Expand
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