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

Juliane Bubeck Wardenburg, Rajita Pappu, Jia Ying Bu, Bruce Mayer, Jonathan Chernoff, David Straus, Andrew C. Chan

Research output: Contribution to journalArticlepeer-review

240 Scopus citations


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

Original languageEnglish
Pages (from-to)607-616
Number of pages10
Issue number5
StatePublished - Nov 1998


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