p21-activated Kinase1(PAK1) can promote ERK activation in a kinase independent manner

TY - JOUR

T1 - p21-activated Kinase1(PAK1) can promote ERK activation in a kinase independent manner

AU - Wang, Zhipeng

AU - Fu, Meng

AU - Wang, Lifeng

AU - Liu, Juanjuan

AU - Li, Yuhua

AU - Brakebusch, Cord

AU - Mei, Qibing

PY - 2013/7/5

Y1 - 2013/7/5

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.M112.426023

DO - 10.1074/jbc.M112.426023

M3 - Journal article

C2 - 23653349

SN - 0021-9258

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

ER -