Raf-1 regulates Rho signaling and cell migration

Raf kinases relay signals inducing proliferation, differentiation, and survival. The Raf-1 isoform has been extensively studied as the upstream kinase linking Ras activation to the MEK/ERK module. Recently, however, genetic experiments have shown that Raf-1 plays an essential role in counteracting a...

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Main Authors:	Ehrenreiter, Karin, Piazzolla, Daniela, Velamoor, Vanishree, Sobczak, Izabela, Small, J. Victor, Takeda, Junji, Leung, Thomas, Baccarini, Manuela
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2005
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171799/

id	pubmed-2171799
recordtype	oai_dc
spelling	pubmed-21717992008-03-05 Raf-1 regulates Rho signaling and cell migration Ehrenreiter, Karin Piazzolla, Daniela Velamoor, Vanishree Sobczak, Izabela Small, J. Victor Takeda, Junji Leung, Thomas Baccarini, Manuela Research Articles Raf kinases relay signals inducing proliferation, differentiation, and survival. The Raf-1 isoform has been extensively studied as the upstream kinase linking Ras activation to the MEK/ERK module. Recently, however, genetic experiments have shown that Raf-1 plays an essential role in counteracting apoptosis, and that it does so independently of its ability to activate MEK. By conditional gene ablation, we now show that Raf-1 is required for normal wound healing in vivo and for the migration of keratinocytes and fibroblasts in vitro. Raf-1–deficient cells show a symmetric, contracted appearance, characterized by cortical actin bundles and by a disordered vimentin cytoskeleton. These defects are due to the hyperactivity and incorrect localization of the Rho-effector Rok-α to the plasma membrane. Raf-1 physically associates with Rok-α in wild-type (WT) cells, and reintroduction of either WT or kinase-dead Raf-1 in knockout fibroblasts rescues their defects in shape and migration. Thus, Raf-1 plays an essential, kinase-independent function as a spatial regulator of Rho downstream signaling during migration. The Rockefeller University Press 2005-03-14 /pmc/articles/PMC2171799/ /pubmed/15753127 http://dx.doi.org/10.1083/jcb.200409162 Text en Copyright © 2005, 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/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ehrenreiter, Karin Piazzolla, Daniela Velamoor, Vanishree Sobczak, Izabela Small, J. Victor Takeda, Junji Leung, Thomas Baccarini, Manuela
spellingShingle	Ehrenreiter, Karin Piazzolla, Daniela Velamoor, Vanishree Sobczak, Izabela Small, J. Victor Takeda, Junji Leung, Thomas Baccarini, Manuela Raf-1 regulates Rho signaling and cell migration
author_facet	Ehrenreiter, Karin Piazzolla, Daniela Velamoor, Vanishree Sobczak, Izabela Small, J. Victor Takeda, Junji Leung, Thomas Baccarini, Manuela
author_sort	Ehrenreiter, Karin
title	Raf-1 regulates Rho signaling and cell migration
title_short	Raf-1 regulates Rho signaling and cell migration
title_full	Raf-1 regulates Rho signaling and cell migration
title_fullStr	Raf-1 regulates Rho signaling and cell migration
title_full_unstemmed	Raf-1 regulates Rho signaling and cell migration
title_sort	raf-1 regulates rho signaling and cell migration
description	Raf kinases relay signals inducing proliferation, differentiation, and survival. The Raf-1 isoform has been extensively studied as the upstream kinase linking Ras activation to the MEK/ERK module. Recently, however, genetic experiments have shown that Raf-1 plays an essential role in counteracting apoptosis, and that it does so independently of its ability to activate MEK. By conditional gene ablation, we now show that Raf-1 is required for normal wound healing in vivo and for the migration of keratinocytes and fibroblasts in vitro. Raf-1–deficient cells show a symmetric, contracted appearance, characterized by cortical actin bundles and by a disordered vimentin cytoskeleton. These defects are due to the hyperactivity and incorrect localization of the Rho-effector Rok-α to the plasma membrane. Raf-1 physically associates with Rok-α in wild-type (WT) cells, and reintroduction of either WT or kinase-dead Raf-1 in knockout fibroblasts rescues their defects in shape and migration. Thus, Raf-1 plays an essential, kinase-independent function as a spatial regulator of Rho downstream signaling during migration.
publisher	The Rockefeller University Press
publishDate	2005
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171799/
_version_	1611424716669583360

Raf-1 regulates Rho signaling and cell migration

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