| Autor: |
Nekhoroshkova, Elena, Albert, Stefan, Becker, Matthias, Rapp, Ulf R. |
| Předmět: |
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| Zdroj: |
PLoS ONE; 2009, Vol. 4 Issue 2, p1-18, 18p, 4 Color Photographs, 2 Diagrams, 3 Graphs |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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