Premium
A PAK1–PIX–PKL complex is activated by the T‐cell receptor independent of Nck, Slp‐76 and LAT
Author(s) -
Ku Gregory M.,
Yablonski Deborah,
Manser Edward,
Lim Louis,
Weiss Arthur
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.3.457
Subject(s) - biology , pak1 , receptor , microbiology and biotechnology , signal transduction , genetics
Given the importance of the Rho GTPase family member Rac1 and the Rac1/Cdc42 effector PAK1 in T‐cell activation, we investigated the requirements for their activation by the T‐cell receptor (TCR). Rac1 and PAK1 activation required the tyrosine kinases ZAP‐70 and Syk, but not the cytoplasmic adaptor Slp‐76. Surprisingly, PAK1 was activated in the absence of the transmembrane adaptor LAT while Rac1 was not. However, efficient PAK1 activation required its binding sites for Rho GTPases and for PIX, a guanine nucleotide exchange factor for Rho GTPases. The overexpression of βPIX that either cannot bind PAK1 or lacks GEF function blocked PAK1 activation. These data suggest that a PAK1–PIX complex is recruited to appropriate sites for activation and that PIX is required for Rho family GTPase activation upstream of PAK1. Furthermore, we detected a stable trimolecular complex of PAK1, PIX and the paxillin kinase linker p95PKL. Taken together, these data show that PAK1 contained in this trimolecular complex is activated by a novel LAT‐ and Slp‐76‐independent pathway following TCR stimulation.