Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Amino Acids / analysis
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Animals
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Carrier Proteins / genetics*
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Carrier Proteins / isolation & purification
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Carrier Proteins / physiology*
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Cell Line
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Cloning, Molecular
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Enzyme Precursors / metabolism
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GRB2 Adaptor Protein
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Humans
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Intracellular Signaling Peptides and Proteins
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Isoenzymes / metabolism
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Jurkat Cells / chemistry
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Lymphocyte Activation / physiology
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Membrane Proteins*
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Molecular Sequence Data
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Phosphatidylinositol 3-Kinases / metabolism
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Phospholipase C gamma
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Phosphoproteins / genetics*
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Phosphoproteins / isolation & purification
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Phosphoproteins / physiology*
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Protein-Tyrosine Kinases / metabolism
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Proteins / metabolism
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Rats
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Receptors, Antigen, T-Cell / metabolism
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Sequence Homology, Amino Acid
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Signal Transduction / physiology
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Substrate Specificity
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Syk Kinase
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Tissue Distribution
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Type C Phospholipases / metabolism
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ZAP-70 Protein-Tyrosine Kinase
Substances
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Adaptor Proteins, Signal Transducing
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Amino Acids
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Carrier Proteins
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DNA, Complementary
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Enzyme Precursors
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GRB2 Adaptor Protein
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GRB2 protein, human
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Grb2 protein, rat
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Intracellular Signaling Peptides and Proteins
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Isoenzymes
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LAT protein, human
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Membrane Proteins
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Phosphoproteins
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Proteins
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Receptors, Antigen, T-Cell
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Phosphatidylinositol 3-Kinases
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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Syk protein, rat
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human
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Type C Phospholipases
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Phospholipase C gamma
Associated data
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GENBANK/AF036905
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GENBANK/AF036906
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GENBANK/AF036907