期刊
NATURE CELL BIOLOGY
卷 7, 期 8, 页码 837-843出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb1283
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Ras proteins control the signalling pathways that are responsible for normal growth and malignant transformation(1). Raf protein kinases are direct Ras effector proteins that initiate the mitogen-activated protein kinase (MAPK) cascade(2), which mediates diverse biological functions such as cell growth, survival and differentiation(3). Here we show that prohibitin, a ubiquitously expressed and evolutionarily conserved protein(4) 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.
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