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PLoS One. 2009;4(2):e4647. doi: 10.1371/journal.pone.0004647. Epub 2009 Feb 27.

A-RAF kinase functions in ARF6 regulated endocytic membrane traffic.

Author information

1
Institut für Medizinische Strahlenkunde und Zellforschung, University of Würzburg, Würzburg, Germany.

Abstract

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.

PMID:
19247477
PMCID:
PMC2645234
DOI:
10.1371/journal.pone.0004647
[Indexed for MEDLINE]
Free PMC Article
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