Ras-Raf signaling needs prohibitin.

Krishnaraj Rajalingam; Thomas Rudel

doi:10.4161/cc.4.11.2142

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Ras-Raf signaling needs prohibitin.

Krishnaraj Rajalingam·Thomas Rudel

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Abstract

Prohibitin has been connected to diverse cellular functions including cell cycle control, senescence, apoptosis and stabilization of mitochondrial proteins. By employing a loss of function approach using siRNAs we have demonstrated an unexpected role of PHB in the activation of Raf/MEK/ERK pathway by active Ras and in modulating epithelial cell adhesion and migration. PHB directly interacts with C-Raf and is required for the displacement of 14-3-3 from C-Raf by active Ras to facilitate plasma membrane localization and activation. Further, the adherent complex proteins cadherin and beta-catenin were localized to plasma membrane suggesting stabilized adherent junctions in PHB silenced cells. Our findings demonstrated a function of PHB in the control of a central signaling pathway involved in cell growth and malignant transformation.

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Animals Cell Adhesion Cell Movement Cell Transformation, Neoplastic Humans MAP Kinase Signaling System Prohibitins Proto-Oncogene Proteins c-raf Repressor Proteins ras Proteins Journal Article Research Support, Non-U.S. Gov't Review

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Krishnaraj Rajalingam, Thomas Rudel. 2005-11-01. Ras-Raf signaling needs prohibitin.. https://doi.org/10.4161/cc.4.11.2142

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