SLP-76 coordinates Nck-dependent Wiskott-Aldrich syndrome protein recruitment with Vav-1/Cdc42-dependent Wiskott-Aldrich syndrome protein activation at the T cell-APC contact site

Rong Zeng, Judy L. Cannon, Robert T. Abraham, Michael Way, Daniel D. Billadeau, Julie Bubeck-Wardenberg, Janis K. Burkhardt

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

We have shown previously that Wiskott-Aldrich syndrome protein (WASP) activation at the site of T cell-APC interaction is a two-step process, with recruitment dependent on the proline-rich domain and activation dependent on binding of Cdc42-GTP to the GTPase binding domain. Here, we show that WASP recruitment occurs through binding to the C-terminal Src homology 3 domain of Nck. In contrast, WASP activation requires Vav-1. In Vav-1-deficient T cells, WASP recruitment proceeds normally, but localized activation of Cdc42 and WASP is disrupted. The recruitment and activation of WASP are coordinated by tyrosine-phosphorylated Src homology 2 domain-containing leukocyte protein of 76 kDa, which functions as a scaffold, bringing Nck and WASP into proximity with Vav-1 and Cdc42-GTP. Taken together, these findings reconstruct the signaling pathway leading from TCR ligation to localized WASP activation.

Original languageEnglish (US)
Pages (from-to)1360-1368
Number of pages9
JournalJournal of Immunology
Volume171
Issue number3
DOIs
StatePublished - Aug 1 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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