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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.

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.

SUBMITTER: Nekhoroshkova E

PROVIDER: S-EPMC2645234 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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

Nekhoroshkova Elena E Albert Stefan S Becker Matthias M Rapp Ulf R UR

PloS one 20090227 2

<h4>Background</h4>RAF kinases direct ERK MAPK signaling to distinct subcellular compartments in response to growth factor stimulation.<h4>Methodology/principal findings</h4>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 tubu ...[more]

PMID: 19247477

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