P21-activated kinase 1 (PAK1) can promote ERK activation in a kinase-independent manner

Abstract

PAK1 plays an important role in proliferation and tumorigenesis, at least partially by promoting ERK phosphorylation of C-RAF (Ser-338) or MEK1 (Ser-298). We observed how that overexpression of a kinase-dead mutant form ofPAK1increased phosphorylation of MEK1/2 (Ser-217/Ser-221) and ERK (Thr- 202/Tyr-204), although phosphorylation of B-RAF (Ser-445) and C-RAF (Ser-338) remained unchanged. Furthermore, increased activation of the PAK1 activator Rac1 induced the formation of a triple complex of Rac1, PAK1, and MEK1 independent of the kinase activity of PAK1. These data suggest that PAK1 can stimulateMEKactivity in a kinase-independent manner, probably by serving as a scaffold to facilitate interaction of C-RAF. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.