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

• Autores: M. J. Byrne, Y. Sasahara, R. Rachid
• Localización: Molecular cell, ISSN 1097-2765, Nº 10, 2002, págs. 1269-1282
• Idioma: inglés
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• Resumen

  • 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.