Letter abstract
Nature Cell Biology 7, 837 - 843 (2005)
Published online: 24 July 2005 | doi:10.1038/ncb1283
Prohibitin is required for Ras-induced Raf–MEK–ERK activation and epithelial cell migration
Krishnaraj Rajalingam1, Christian Wunder1, Volker Brinkmann2, Yuri Churin1, Mirko Hekman3, Claudia Sievers1, Ulf R. Rapp3 & Thomas Rudel1
Ras proteins control the signalling pathways that are responsible for normal growth and malignant transformation1. Raf protein kinases are direct Ras effector proteins that initiate the mitogen-activated protein kinase (MAPK) cascade2, which mediates diverse biological functions such as cell growth, survival and differentiation3. Here we show that prohibitin, a ubiquitously expressed and evolutionarily conserved protein4 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 
-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.
- Max Planck Institute for Infection Biology, Department of Molecular Biology, Schumannstr. 21/22, D-10117 Berlin, Germany.
- Microscopy Core Facility, Schumannstr. 21/22, D-10117 Berlin, Germany.
- Institut für Medizinische Strahlenkunde und Zellforschung, University of Würzburg, Versbacher Strasse 5, 97078 Würzburg, Germany.
Correspondence to: Thomas Rudel1 e-mail: rudel@mpiib-berlin.mpg.de
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