Abstract
F-actin polymerization following engagement of the T cell receptor (TCR) is dependent on WASP and is critical for T cell activation. The link between TCR and WASP is not fully understood. In resting cells, WASP exists in a complex with WIP, which inhibits its activation by Cdc42. We show that the adaptor protein CrkL binds directly to WIP. Further, TCR ligation results in the formation of a ZAP-70-CrkL-WIP-WASP complex, which is recruited to lipid rafts and the immunological synapse. TCR engagement also causes PKCtheta-dependent phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP complex, thereby releasing it from WIP inhibition. These results suggest that the ZAP-70-CrkL-WIP pathway and PKCtheta link TCR to WASP activation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism
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Animals
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B-Lymphocytes / immunology
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Carrier Proteins / immunology
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Cell Line
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Cytoskeletal Proteins
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Humans
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Intracellular Signaling Peptides and Proteins
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Jurkat Cells
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Kinetics
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Mice
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Mice, Knockout
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Protein Kinase C / deficiency
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Protein Kinase C / genetics
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Protein Kinase C / metabolism
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Protein Kinase C beta
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Protein Transport
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Proteins / immunology*
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocytes / immunology
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Tumor Cells, Cultured
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Wiskott-Aldrich Syndrome / immunology
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Wiskott-Aldrich Syndrome / metabolism
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Wiskott-Aldrich Syndrome Protein
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cdc42 GTP-Binding Protein / antagonists & inhibitors
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cdc42 GTP-Binding Protein / metabolism
Substances
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Actins
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Carrier Proteins
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Cytoskeletal Proteins
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Intracellular Signaling Peptides and Proteins
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Proteins
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Receptors, Antigen, T-Cell
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WAS protein, human
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WIPF1 protein, human
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Was protein, mouse
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Waspip protein, mouse
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Wiskott-Aldrich Syndrome Protein
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Protein Kinase C
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Protein Kinase C beta
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cdc42 GTP-Binding Protein