| First Author | Rouquette-Jazdanian AK | Year | 2012 |
| Journal | Mol Cell | Volume | 48 |
| Issue | 2 | Pages | 298-312 |
| PubMed ID | 22981863 | Mgi Jnum | J:191280 |
| Mgi Id | MGI:5461403 | Doi | 10.1016/j.molcel.2012.08.011 |
| Citation | Rouquette-Jazdanian AK, et al. (2012) LAT-independent Erk activation via Bam32-PLC-gamma1-Pak1 complexes: GTPase-independent Pak1 activation. Mol Cell 48(2):298-312 |
| abstractText | 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-gamma1-Pak1 complexes, in which Pak1 kinase activates Raf-1 and Mek-1, both upstream of Erk. In the Bam32-PLC-gamma1-Pak1 complex, catalytically inactive PLC-gamma1 is used as a scaffold linking Bam32 to Pak1. PLC-gamma1(C-SH2) directly binds S141 of Bam32, preventing LAT-mediated activation of Ras by PLC-gamma1. The Bam32-PLC-gamma1 interaction enhances the binding of the SH3 domain of the phospholipase with Pak1. The PLC-gamma1(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-gamma1 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. |
