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

Immunity. 2001 Aug;15(2):249-59. doi: 10.1016/s1074-7613(01)00178-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen-Presenting Cells / metabolism*
  • Cell Compartmentation
  • Humans
  • Intercellular Junctions / metabolism*
  • Jurkat Cells
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
  • Models, Biological
  • Proline
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / isolation & purification
  • Proteins / metabolism*
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction
  • T-Lymphocytes / metabolism*
  • Wiskott-Aldrich Syndrome Protein
  • ZAP-70 Protein-Tyrosine Kinase
  • cdc42 GTP-Binding Protein / isolation & purification
  • cdc42 GTP-Binding Protein / metabolism*

Substances

  • Proteins
  • Receptors, Antigen, T-Cell
  • WAS protein, human
  • Wiskott-Aldrich Syndrome Protein
  • Proline
  • Protein-Tyrosine Kinases
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • cdc42 GTP-Binding Protein