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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2009
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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) |
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Medicine R Science Q Elena Nekhoroshkova Stefan Albert Matthias Becker Ulf R Rapp A-RAF kinase functions in ARF6 regulated endocytic membrane traffic. |
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<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 |
work_keys_str_mv |
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1718413965512409088 |