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

<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...

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Autores principales: Elena Nekhoroshkova, Stefan Albert, Matthias Becker, Ulf R Rapp
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Publicado: Public Library of Science (PLoS) 2009
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spelling oai:doaj.org-article:0bdac0f91c3c4d48afbb205d0c60fa7e2021-11-25T06:17:02ZA-RAF kinase functions in ARF6 regulated endocytic membrane traffic.1932-620310.1371/journal.pone.0004647https://doaj.org/article/0bdac0f91c3c4d48afbb205d0c60fa7e2009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19247477/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<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 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.<h4>Conclusions/significance</h4>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.Elena NekhoroshkovaStefan AlbertMatthias BeckerUlf R RappPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 2, p e4647 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Elena Nekhoroshkova
Stefan Albert
Matthias Becker
Ulf R Rapp
A-RAF kinase functions in ARF6 regulated endocytic membrane traffic.
description <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 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.<h4>Conclusions/significance</h4>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.
format article
author Elena Nekhoroshkova
Stefan Albert
Matthias Becker
Ulf R Rapp
author_facet Elena Nekhoroshkova
Stefan Albert
Matthias Becker
Ulf R Rapp
author_sort Elena Nekhoroshkova
title A-RAF kinase functions in ARF6 regulated endocytic membrane traffic.
title_short A-RAF kinase functions in ARF6 regulated endocytic membrane traffic.
title_full A-RAF kinase functions in ARF6 regulated endocytic membrane traffic.
title_fullStr A-RAF kinase functions in ARF6 regulated endocytic membrane traffic.
title_full_unstemmed A-RAF kinase functions in ARF6 regulated endocytic membrane traffic.
title_sort a-raf kinase functions in arf6 regulated endocytic membrane traffic.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/0bdac0f91c3c4d48afbb205d0c60fa7e
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AT matthiasbecker arafkinasefunctionsinarf6regulatedendocyticmembranetraffic
AT ulfrrapp arafkinasefunctionsinarf6regulatedendocyticmembranetraffic
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