LAT-independent Erk activation via Bam32-PLC-?1-Pak1 complexes: GTPase-independent Pak1 activation.

ABSTRACT: In T cells, the adaptor Bam32 is coupled to Erk activation downstream of the TCR by an unknown mechanism. We characterized in Jurkat cells and primary T lymphocytes a pathway dependent on Bam32-PLC-?1-Pak1 complexes, in which Pak1 kinase activates Raf-1 and Mek-1, both upstream of Erk. In the Bam32-PLC-?1-Pak1 complex, catalytically inactive PLC-?1 is used as a scaffold linking Bam32 to Pak1. PLC-?1(C-SH2) directly binds S141 of Bam32, preventing LAT-mediated activation of Ras by PLC-?1. The Bam32-PLC-?1 interaction enhances the binding of the SH3 domain of the phospholipase with Pak1. The PLC-?1(SH3)-Pak1 interaction activates Pak1 independently of the small GTPases Rac1/Cdc42, previously described as being the only activators of Pak1 in T cells. Direct binding of the SH3 domain of PLC-?1 to Pak1 dissociates inactive Pak1 homodimers, a mechanism required for Pak1 activation. We have thus uncovered a LAT/Ras-independent, Bam32-nucleated pathway that activates Erk signaling in T cells.

SUBMITTER: Rouquette-Jazdanian AK 

PROVIDER: S-EPMC3483363 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature