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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents



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ID: 474488.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
A-RAF kinase functions in ARF6 regulated endocytic membrane traffic
Authors:Nekhoroshkova, E.; Albert, S.; Becker, M.; Rapp, U. R.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:PLoS ONE
Volume:4
Issue / Number:2
Start Page:e4647
Audience:Not Specified
Abstract / Description:BACKGROUND: RAF kinases direct ERK MAPK signaling to distinct subcellular compartments in response to growth factor stimulation. METHODOLOGY/PRINCIPAL FINDINGS: Of the three mammalian isoforms A-RAF is special in that one of its two lipid binding domains mediates a unique pattern of membrane localization. Specific membrane binding is retained by an N-terminal fragment (AR149) that corresponds to a naturally occurring splice variant termed DA-RAF2. AR149 colocalizes with ARF6 on tubular endosomes and has a dominant negative effect on endocytic trafficking. Moreover actin polymerization of yeast and mammalian cells is abolished. AR149/DA-RAF2 does not affect the internalization step of endocytosis, but trafficking to the recycling compartment. CONCLUSIONS/SIGNIFICANCE: A-RAF induced ERK activation is required for this step by activating ARF6, as A-RAF depletion or inhibition of the A-RAF controlled MEK-ERK cascade blocks recycling. These data led to a new model for A-RAF function in endocytic trafficking.
Free Keywords:ADP-Ribosylation Factors/*physiology; Animals; Cell Line; Cell Membrane/enzymology/metabolism; Endocytosis/*physiology; Enzyme Activation; Fluorescent Antibody Technique, Indirect; Humans; Microscopy, Fluorescence; Proto-Oncogene Proteins A-raf/*metabolism; RNA, Small Interfering
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Institut fur Medizinische Strahlenkunde und Zellforschung, University of Wurzburg, Wurzburg, Germany.
Identifiers:ISSN:1932-6203 (Electronic)
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=..
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