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~1

摘要

We have shown previously that wiskott-Aldrich syndrome protein (WASP) activation at the site of T cell-APC interaction is a tow-step process, with recruitment dependent on the proline-rich domain and activation dependent on binding of Cdc24-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 tyrosinephosphorylated 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. Thken together, these findings reconstruct the signaling pathway leading from TCR ligation to localized WASP activation.