Mechanism of Recruitment of WASP to the Immunological Synapse and of Its Activation Following TCR Ligation

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 ad...

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Veröffentlicht in:	Molecular cell 2002-12, Vol.10 (6), p.1269-1281
Hauptverfasser:	Sasahara, Yoji, Rachid, Rima, Byrne, Michael J., de la Fuente, Miguel A., Abraham, Robert T., Ramesh, Narayanaswamy, Geha, Raif S.
Format:	Artikel
Sprache:	eng
Schlagworte:	Actins - metabolism Animals B-Lymphocytes - immunology Carrier Proteins - immunology cdc42 GTP-Binding Protein - antagonists & inhibitors cdc42 GTP-Binding Protein - metabolism Cell Line Cytoskeletal Proteins Humans Intracellular Signaling Peptides and Proteins Jurkat Cells Kinetics Mice Mice, Knockout Protein Kinase C - deficiency Protein Kinase C - genetics Protein Kinase C - metabolism Protein Kinase C beta Protein Transport Proteins - immunology Receptors, Antigen, T-Cell - immunology Receptors, Antigen, T-Cell - metabolism T-Lymphocytes - immunology Tumor Cells, Cultured Wiskott-Aldrich Syndrome - immunology Wiskott-Aldrich Syndrome - metabolism Wiskott-Aldrich Syndrome Protein
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Zusammenfassung:	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 PKCθ-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 PKCθ link TCR to WASP activation.
ISSN:	1097-2765 1097-4164
DOI:	10.1016/S1097-2765(02)00728-1