p21 activated kinase 5 activates Raf-1 and targets it to mitochondria.

Article Details


Wu X, Carr HS, Dan I, Ruvolo PP, Frost JA

p21 activated kinase 5 activates Raf-1 and targets it to mitochondria.

J Cell Biochem. 2008 Sep 1;105(1):167-75. doi: 10.1002/jcb.21809.

PubMed ID
18465753 [ View in PubMed

Raf-1 is an important effector of Ras mediated signaling and is a critical regulator of the ERK/MAPK pathway. Raf-1 activation is controlled in part by phosphorylation on multiple residues, including an obligate phosphorylation site at serine 338. Previously PAK1 and casein kinase II have been implicated as serine 338 kinases. To identify novel kinases that phosphorylate this site, we tested the ability of group II PAKs (PAKs 4-6) to control serine 338 phosphorylation. We observed that all group II PAKs were efficient serine 338 kinases, although only PAK1 and PAK5 significantly stimulated Raf-1 kinase activity. We also showed that PAK5 forms a tight complex with Raf-1 in the cell, but not A-Raf or B-Raf. Importantly, we also demonstrated that the association of Raf-1 with PAK5 targets a subpopulation of Raf-1 to mitochondria. These data indicate that PAK5 is a potent regulator of Raf-1 activity and may control Raf-1 dependent signaling at mitochondria.

DrugBank Data that Cites this Article

NameUniProt ID
RAF proto-oncogene serine/threonine-protein kinaseP04049Details
Serine/threonine-protein kinase PAK 5Q9P286Details