Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation

Yoji Sasahara, Rima Rachid, Michael J. Byrne, Miguel A. De la Fuente, Robert T. Abraham, Narayanaswamy Ramesh, Raif S. Geha

Research output: Contribution to journalArticlepeer-review

205 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1269-1281
Number of pages13
JournalMolecular Cell
Volume10
Issue number6
DOIs
Publication statusPublished - 2002 Dec 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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