Dephosphorylation of Ser-259 regulates Raf-1 membrane association

Autor(en)

Markus Kubicek, Margit Pacher, Dietmar Abraham, Klaus Podar, Manfred Eulitz, Manuela Baccarini

Abstrakt

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.

Organisation(en)

Externe Organisation(en)

Helmholtz-Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

Journal

Journal of Biological Chemistry

Band

277

Seiten

7913-7919

Anzahl der Seiten

7

ISSN

0021-9258

DOI

https://doi.org/10.1074/jbc.M108733200

Publikationsdatum

2002

Peer-reviewed

Ja

ÖFOS 2012

1060 Biologie

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/dephosphorylation-of-ser259-regulates-raf1-membrane-association(9cb47477-b5f1-4fc8-a58c-c32f9004d7a0).html