Dephosphorylation of Ser-259 regulates Raf-1 membrane association.

Article Details


Kubicek M, Pacher M, Abraham D, Podar K, Eulitz M, Baccarini M

Dephosphorylation of Ser-259 regulates Raf-1 membrane association.

J Biol Chem. 2002 Mar 8;277(10):7913-9. Epub 2001 Dec 27.

PubMed ID
11756411 [ View in PubMed

Mitogenic stimulation of Raf-1 is a complex yet incompletely understood process involving membrane relocalization and phosphorylation of activating residues. We recently reported that Raf-1-associated protein phosphatase 2A contributes to kinase activation, an effect mediated via Ser-259 of Raf-1. Here, we show that mitogens stimulate Ser-259 dephosphorylation and Raf-1/protein phosphatase 2A association concomitantly with membrane accumulation and activation of Raf-1. Blocking Ser-259 dephosphorylation inhibits the two latter events, but it does not prevent activation of a S259A Raf-1 mutant, which is preferentially localized at the membrane independently of mitogenic stimulation. Inhibition of Ser-259 dephosphorylation has no effect on the activation of membrane-tethered Raf-1 (Raf-1CAAX). These data show that Ser-259 dephosphorylation contributes to Raf-1 activation by supporting its membrane accumulation rather than by increasing the specific activity of the kinase and provide a mechanistic basis for the support of kinase activation by Raf-1-associated protein phosphatase 2A.

DrugBank Data that Cites this Article

NameUniProt ID
RAF proto-oncogene serine/threonine-protein kinaseP04049Details