WASP recruitment to the T cell:APC contact site occurs independently of Cdc42 activation

Judy L. Cannon, Christine M. Labno, Gerra Bosco, Abhinav Seth, Mary H K McGavin, Katherine A. Siminovitch, Michael K. Rosen, Janis K. Burkhardt

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

Cdc42 and WASP are critical regulators of actin polymerization whose function during T cell signaling is poorly understood. Using a novel reagent that specifically detects Cdc42-GTP in fixed cells, we found that activated Cdc42 localizes to the T cell:APC contact site in an antigen-dependent manner. TCR signaling alone was sufficient to induce localization of Cdc42-GTP, and functional Lck and Zap-70 kinases were required. WASP also localized to the T cell:APC contact site in an antigen-dependent manner. Surprisingly, WASP localization was independent of the Cdc42 binding domain but required the proline-rich domain. Our results indicate that localized WASP activation requires the integration of multiple signals: WASP is recruited via interaction with SH3 domain-containing proteins and is activated by Cdc42-GTP concentrated at the same site.

Original languageEnglish (US)
Pages (from-to)249-259
Number of pages11
JournalImmunity
Volume15
Issue number2
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Cannon, J. L., Labno, C. M., Bosco, G., Seth, A., McGavin, M. H. K., Siminovitch, K. A., Rosen, M. K., & Burkhardt, J. K. (2001). WASP recruitment to the T cell:APC contact site occurs independently of Cdc42 activation. Immunity, 15(2), 249-259. https://doi.org/10.1016/S1074-7613(01)00178-9