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Raf-1 activation disrupts its binding to keratins during cell stress

Keratins 8 and 18 (K8/18) heteropolymers may regulate cell signaling via the known K18 association with 14-3-3 proteins and 14-3-3 association with Raf-1 kinase. We characterized Raf–keratin–14-3-3 associations and show that Raf associates directly with K8, independent of Raf kinase activity or Ras–...

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Detalles Bibliográficos
Autores principales: Ku, Nam-On, Fu, Haian, Omary, M. Bishr
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172217/
https://www.ncbi.nlm.nih.gov/pubmed/15314064
http://dx.doi.org/10.1083/jcb.200402051
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author Ku, Nam-On
Fu, Haian
Omary, M. Bishr
author_facet Ku, Nam-On
Fu, Haian
Omary, M. Bishr
author_sort Ku, Nam-On
collection PubMed
description Keratins 8 and 18 (K8/18) heteropolymers may regulate cell signaling via the known K18 association with 14-3-3 proteins and 14-3-3 association with Raf-1 kinase. We characterized Raf–keratin–14-3-3 associations and show that Raf associates directly with K8, independent of Raf kinase activity or Ras–Raf interaction, and that K18 is a Raf physiologic substrate. Raf activation during oxidative and toxin exposure in cultured cells and animals disrupt keratin–Raf association in a phosphorylation-dependent manner. Mutational analysis showed that 14-3-3 residues that are essential for Raf binding also regulate 14-3-3–keratin association. Similarly, Raf phosphorylation sites that are important for binding to 14-3-3 are also essential for Raf binding to K8/18. Therefore, keratins may modulate some aspects of Raf signaling under basal conditions via sequestration by K8, akin to Raf–14-3-3 binding. Keratin-bound Raf kinase is released upon Raf hyperphosphorylation and activation during oxidative and other stresses.
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spelling pubmed-21722172008-03-05 Raf-1 activation disrupts its binding to keratins during cell stress Ku, Nam-On Fu, Haian Omary, M. Bishr J Cell Biol Research Articles Keratins 8 and 18 (K8/18) heteropolymers may regulate cell signaling via the known K18 association with 14-3-3 proteins and 14-3-3 association with Raf-1 kinase. We characterized Raf–keratin–14-3-3 associations and show that Raf associates directly with K8, independent of Raf kinase activity or Ras–Raf interaction, and that K18 is a Raf physiologic substrate. Raf activation during oxidative and toxin exposure in cultured cells and animals disrupt keratin–Raf association in a phosphorylation-dependent manner. Mutational analysis showed that 14-3-3 residues that are essential for Raf binding also regulate 14-3-3–keratin association. Similarly, Raf phosphorylation sites that are important for binding to 14-3-3 are also essential for Raf binding to K8/18. Therefore, keratins may modulate some aspects of Raf signaling under basal conditions via sequestration by K8, akin to Raf–14-3-3 binding. Keratin-bound Raf kinase is released upon Raf hyperphosphorylation and activation during oxidative and other stresses. The Rockefeller University Press 2004-08-16 /pmc/articles/PMC2172217/ /pubmed/15314064 http://dx.doi.org/10.1083/jcb.200402051 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Ku, Nam-On
Fu, Haian
Omary, M. Bishr
Raf-1 activation disrupts its binding to keratins during cell stress
title Raf-1 activation disrupts its binding to keratins during cell stress
title_full Raf-1 activation disrupts its binding to keratins during cell stress
title_fullStr Raf-1 activation disrupts its binding to keratins during cell stress
title_full_unstemmed Raf-1 activation disrupts its binding to keratins during cell stress
title_short Raf-1 activation disrupts its binding to keratins during cell stress
title_sort raf-1 activation disrupts its binding to keratins during cell stress
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172217/
https://www.ncbi.nlm.nih.gov/pubmed/15314064
http://dx.doi.org/10.1083/jcb.200402051
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