1 Section of Molecular Pathology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet2 BRIC, BRIC, Københavns Universitet3 Ploug Group, BRIC Research Groups, BRIC, Københavns Universitet4 unknown5 Brakebusch Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet6 Ploug Group, BRIC Research Groups, BRIC, Københavns Universitet7 Brakebusch Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet
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 now that overexpression of a kinase-dead mutant form of PAK1 increased phosphorylation of Mek1/2 (Ser 217/221) and Erk (Thr 202/Tyr 204) although phosphorylation of b-Raf (Ser445) 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.