title: A-RAF kinase functions in ARF6 regulated endocytic membrane traffic.
abstract: BACKGROUND
  RAF kinases direct ERK MAPK signaling to distinct subcellular compartments in response to growth factor stimulation.
  
  
  RESULTS
  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
  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.
authors.affiliation: Institut für Medizinische Strahlenkunde und Zellforschung, University of Würzburg, Würzburg, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Nekhoroshkova
authors.forename: Stefan
authors.initials: S
authors.lastname: Albert
authors.forename: Matthias
authors.initials: M
authors.lastname: Becker
authors.forename: Ulf R
authors.initials: UR
authors.lastname: Rapp
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D004789:Enzyme Activation; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008856:Microscopy, Fluorescence; D048491:Proto-Oncogene Proteins A-raf / Q000378:metabolism*; D034741:RNA, Small Interfering
chemical_list: D000089982:ADP-Ribosylation Factor 6; D034741:RNA, Small Interfering; D048491:Proto-Oncogene Proteins A-raf; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human