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

Abstract

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 β-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.

Cite this article

Rajalingam, K., Wunder, C., Brinkmann, V. et al. Prohibitin is required for Ras-induced Raf–MEK–ERK activation and epithelial cell migration. Nat Cell Biol 7, 837–843 (2005). https://doi.org/10.1038/ncb1283

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