p21-activated kinase 1 (PAK1) can promote ERK activation in a kinase-independent manner.

Titlep21-activated kinase 1 (PAK1) can promote ERK activation in a kinase-independent manner.
Publication TypeJournal Article
Year of Publication2013
AuthorsWang Z, Fu M, Wang L, Liu J, Li Y, Brakebusch C, Mei Q
JournalThe Journal of biological chemistry
Volume288
Issue27
Pagination20093-9
Date Published2013 Jul 5
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 of PAK1 increased 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 stimulate MEK activity in a kinase-independent manner, probably by serving as a scaffold to facilitate interaction of C-RAF.

DOI10.1107/S1600536813013056
Alternate JournalJ. Biol. Chem.