Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76

Tyrosine phosphorylation of linker proteins enables the T cell antigen rece ptor (TCR)-associated protein tyrosine kinases to phosphorylate and regulat e effector molecules that generate second messengers. We demonstrate here t hat the SLP-76 linker protein interacts with both nck, an adaptor protein, and Vav, a guanine nucleotide exchange factor for Rho-family GTPases. The a ssembly of this tri-molecular complex permits the activated Rho-family GTPa ses to regulate target effecters that interact through nck. In turn, assemb ly of this complex mediates the enzymatic activation of the p21-activated p rotein kinase 1 and facilitates actin polymerization. Hence, phosphorylatio n of linker proteins not only bridges the TCR-associated PTK, ZAP-70, with downstream effector proteins, but also provides a scaffold to integrate dis tinct signaling complexes to regulate T cell function.