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

Mol Cell. 2002 Dec;10(6):1269-81. doi: 10.1016/s1097-2765(02)00728-1.


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 PKCtheta-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 PKCtheta link TCR to WASP activation.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • B-Lymphocytes / immunology
  • Carrier Proteins / immunology
  • Cell Line
  • Cytoskeletal Proteins
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Jurkat Cells
  • Kinetics
  • Mice
  • Mice, Knockout
  • Protein Kinase C / deficiency
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Protein Kinase C beta
  • Protein Transport
  • Proteins / immunology*
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / immunology
  • Tumor Cells, Cultured
  • Wiskott-Aldrich Syndrome / immunology
  • Wiskott-Aldrich Syndrome / metabolism
  • Wiskott-Aldrich Syndrome Protein
  • cdc42 GTP-Binding Protein / antagonists & inhibitors
  • cdc42 GTP-Binding Protein / metabolism


  • Actins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Receptors, Antigen, T-Cell
  • WAS protein, human
  • WIPF1 protein, human
  • Was protein, mouse
  • Waspip protein, mouse
  • Wiskott-Aldrich Syndrome Protein
  • Protein Kinase C
  • Protein Kinase C beta
  • cdc42 GTP-Binding Protein