Cutting edge: WIP, a binding partner for Wiskott-Aldrich syndrome protein,cooperates with Vav in the regulation of T cell activation

Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP), specific ally binds to a region of WASp that is frequently mutated in Wiskott-Aldric h syndrome. Due to the similar phenotypes of WASp and Vav-deficient T cells , and the putative importance of the WIP/WASp complex in mediating normal s ignals from the TCR, we investigated the role of WIP in regulating NF-AT/AP -1-mediated gene transcription, We show that WIP has the ability to enhance Vav-mediated activation of NF-AT/AP-1 gene transcription. In addition, we provide evidence that the interaction of WIP with WASp is necessary, but no t sufficient for the ability of WIP to regulate NF-AT/AP-1 activity. Finall y, we have identified a region in WIP required for its regulation of NP-AT/ AP-1 activity. Our data suggests that the WIP-WASp interaction is important for NF-AT/AP-1-mediated gene transcription, and that defects seen in the a ctivation of T cells from WAS patients may be due to the inability of these cells to form a functional WIP/WASp-signaling complex.