LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation.
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 this protein is phosphorylated by ZAP-70/Syk protein tyrosine kinases leading to recruitment of multiple signaling molecules. Its function is demonstrated by inhibition of T cell activation following overexpression of a mutant form lacking critical tyrosine residues. Therefore, we propose to name the molecule LAT-linker for activation of T cells.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Amino Acids, Animals, Carrier Proteins, Cell Line, Cloning, Molecular, DNA, Complementary, Enzyme Precursors, GRB2 Adaptor Protein, Humans, Intracellular Signaling Peptides and Proteins, Isoenzymes, Jurkat Cells, Lymphocyte Activation, Membrane Proteins, Molecular Sequence Data, Phospholipase C gamma, Phosphoproteins, Protein-Tyrosine Kinases, Proteins, Rats, Receptors, Antigen, T-Cell, Sequence Homology, Amino Acid, Signal Transduction, Substrate Specificity, Tissue Distribution, Type C Phospholipases, ZAP-70 Protein-Tyrosine Kinase
1-Phosphatidylinositol 3-Kinase, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Amino Acids, Animals, Carrier Proteins, Cell Line, Cloning, Molecular, DNA, Complementary, Enzyme Precursors, GRB2 Adaptor Protein, Humans, Intracellular Signaling Peptides and Proteins, Isoenzymes, Jurkat Cells, Lymphocyte Activation, Membrane Proteins, Molecular Sequence Data, Phospholipase C gamma, Phosphoproteins, Protein-Tyrosine Kinases, Proteins, Rats, Receptors, Antigen, T-Cell, Sequence Homology, Amino Acid, Signal Transduction, Substrate Specificity, Tissue Distribution, Type C Phospholipases, ZAP-70 Protein-Tyrosine Kinase
Cell
Date: Jan. 09, 1998
PubMed ID: 9489702
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