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

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

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BackgroundRAF kinases direct ERK MAPK signaling to distinct subcellular compartments in response to growth factor stimulation.Methodology/principal findingsOf the three mammalian isoforms A-RAF is special in that Home Coffee Machines 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 Foot Protection 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/significanceA-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.