Ras-Raf signaling needs prohibitin.
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.
Rajalingam
Krishnaraj
K
Department of Molecular Biology, Max Planck Institute for Infection Biology, Schumannstr. 21/22, D-10117 Berlin, Germany.
Rudel
Thomas
T
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D000091402:Prohibitins; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D018631:ras Proteins / Q000502:physiology*
C000717328:PHB protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins