p21-activated Kinase1(PAK1) can promote ERK activation in a kinase independent manner
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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.
Original language | English |
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Journal | Journal of Biological Chemistry |
ISSN | 0021-9258 |
DOIs | |
Publication status | Published - 7 May 2013 |
ID: 45826113