Abstract
To elucidate the process of TCR-mediated signaling pathways in lipid rafts, we constructed a chimeric molecule that localizes activated SHP-1 to rafts. Raft targeting of activated SHP-1 in Jurkat-derived transfectants completely inhibited the expression of CD69 and transcriptional factors after TCR cross-linking. 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. Intriguingly, recruitment of endogenous SHP-1 to rafts and its association with LAT were dramatically increased after TCR engagement, suggesting that SHP-1 is involved in raft-mediated T cell activation.
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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Binding Sites
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Calcium / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Carrier Proteins / metabolism
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Enzyme Activation
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Humans
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Intracellular Signaling Peptides and Proteins
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Jurkat Cells
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Lymphocyte Activation / immunology
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Membrane Microdomains / immunology*
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Membrane Proteins / immunology*
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Palmitates / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / immunology
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / immunology*
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Protein Tyrosine Phosphatases / metabolism
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Receptors, Antigen, T-Cell / immunology*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Signal Transduction / immunology*
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T-Lymphocytes / immunology
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Transfection
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Tyrosine / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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LAT protein, human
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Membrane Proteins
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Palmitates
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Phosphoproteins
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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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Tyrosine
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PTPN11 protein, human
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PTPN6 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Calcium