Abstract
Phosphatidylinositol lipid signaling cascades are integral part of TCR-CD3 signaling. The mechanisms by which phosphatidylinositol kinases are coupled to TCR-CD3 complex remain elusive. Here we report an association of type II PtdIns 4-kinase with TCR-CD3 zeta chain upon cross-linking. Mapping studies have revealed that the C-terminal ITAM is critical for docking of the enzyme on the zeta chain. The association is shown to be tyrosyl phosphorylation dependent as mutation of Y-151 and Y-142 on the C-terminal ITAM disrupts interaction of the two proteins. Identification of the associated type II PtdIns 4-kinase revealed that the beta isoform of the enzyme interacts with the zeta chain in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Phosphatidylinositol 4-Kinase / chemistry
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1-Phosphatidylinositol 4-Kinase / metabolism*
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Amino Acid Motifs
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Antibodies, Monoclonal / immunology
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Enzyme Activation
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Humans
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Immunologic Capping
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Jurkat Cells
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Lymphocytes / metabolism
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Membrane Proteins / chemistry
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Membrane Proteins / metabolism*
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Mutagenesis, Site-Directed
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Phosphorylation
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Phosphotyrosine / chemistry
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Protein Interaction Mapping
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Protein Processing, Post-Translational
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Receptors, Antigen, T-Cell / chemistry
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Receptors, Antigen, T-Cell / metabolism*
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Recombinant Fusion Proteins / metabolism
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Transfection
Substances
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Antibodies, Monoclonal
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Membrane Proteins
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins
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antigen T cell receptor, zeta chain
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Phosphotyrosine
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1-Phosphatidylinositol 4-Kinase