NDLI: Isoform-specific interaction of C-RAF with mitochondria.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fueller, Jochen Wittig, Ilka Flatau, Gilles Doye, Anne Santel, Ansgar Rapp, Ulf R. Krohne, Georg Rolando, Monica Lemichez, Emmanuel Galmiche, Antoine
Description	Author Affiliation: Galmiche A ( Institut für Medizinische Strahlenkunde und Zellforschung, University of Würzburg, Würzburg, Germany. antoine.galmiche@mail.uni-wuerzburg.de)
Abstract	The proteins of the RAF family (A-RAF, B-RAF, and C-RAF) are serine/threonine kinases that play important roles in development, mature cell regulation, and cancer. Although it is widely held that their localization on membranes is an important aspect of their function, there are few data that address this aspect of their mode of action. Here, we report that each member of the RAF family exhibits a specific distribution at the level of cellular membranes and that C-RAF is the only isoform that directly targets mitochondria. We found that the RAF kinases exhibit intrinsic differences in terms of mitochondrial affinity and that C-RAF is the only isoform that binds this organelle efficiently. This affinity is conferred by the C-RAF amino-terminal domain and does not depend on the presence of RAS GTPases on the surface of mitochondria. Finally, we analyzed the consequences of C-RAF activation on mitochondria and observed that this event dramatically changes their morphology and their subcellular distribution. Our observations indicate that: (i) RAF kinases exhibit different localizations at the level of cellular membranes; (ii) C-RAF is the only isoform that directly binds mitochondria; and (iii) through its functional coupling with MEK, C-RAF regulates the shape and the cellular distribution of mitochondria.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	21
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-05-23
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Mitochondria Enzymology Proto-Oncogene Proteins C-raf Metabolism Animals Cell Membrane Cells, Cultured Isoenzymes Mice Mice, Knockout Mitogen-Activated Protein Kinase Kinases Protein Binding Deficiency Genetics Substrate Specificity Ras Proteins Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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