Format

Send to

Choose Destination
Nat Cell Biol. 2005 Aug;7(8):837-43. Epub 2005 Jul 24.

Prohibitin is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migration.

Author information

1
Department of Molecular Biology, Max Planck Institute for Infection Biology, Schumannstrasse 21/22, D-10117 Berlin, Germany.

Abstract

Ras proteins control the signalling pathways that are responsible for normal growth and malignant transformation. Raf protein kinases are direct Ras effector proteins that initiate the mitogen-activated protein kinase (MAPK) cascade, which mediates diverse biological functions such as cell growth, survival and differentiation. Here we show that prohibitin, a ubiquitously expressed and evolutionarily conserved protein is indispensable for the activation of the Raf-MEK-ERK pathway by Ras. The membrane targeting and activation of C-Raf by Ras needs prohibitin in vivo. In addition, direct interaction with prohibitin is required for C-Raf activation. C-Raf kinase fails to interact with the active Ras induced by epidermal growth factor in the absence of prohibitin. Moreover, in prohibitin-deficient cells the adhesion complex proteins cadherin and beta-catenin relocalize to the plasma membrane and thereby stabilize adherens junctions. Our data show an unexpected role of prohibitin in the activation of the Ras-Raf signalling pathway and in modulating epithelial cell adhesion and migration.

PMID:
16041367
DOI:
10.1038/ncb1283
[Indexed for MEDLINE]
Free full text

Publication type, MeSH terms, Substances

Publication type

MeSH terms

Substances

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center