Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function

Transformation of fibroblasts by oncogenic Src causes disruption of actin stress fibers and formation of invasive adhesions called podosomes. Because the small GTPase Rho stimulates stress fiber formation, Rho inactivation by Src has been thought to be necessary for stress fiber disruption. However,...

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Main Authors:	Berdeaux, Rebecca L., Díaz, Begoña, Kim, Lomi, Martin, G. Steven
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2004
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172255/

id	pubmed-2172255
recordtype	oai_dc
spelling	pubmed-21722552008-03-05 Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function Berdeaux, Rebecca L. Díaz, Begoña Kim, Lomi Martin, G. Steven Research Articles Transformation of fibroblasts by oncogenic Src causes disruption of actin stress fibers and formation of invasive adhesions called podosomes. Because the small GTPase Rho stimulates stress fiber formation, Rho inactivation by Src has been thought to be necessary for stress fiber disruption. However, we show here that Rho[GTP] levels do not decrease after transformation by activated Src. Inactivation of Rho in Src-transformed fibroblasts by dominant negative RhoA or the Rho-specific inhibitor C3 exoenzyme disrupted podosome structure as judged by localization of podosome components F-actin, cortactin, and Fish. Inhibition of Rho strongly inhibited Src-induced proteolytic degradation of the extracellular matrix. Furthermore, development of an in situ Rho[GTP] affinity assay allowed us to detect endogenous Rho[GTP] at podosomes, where it colocalized with F-actin, cortactin, and Fish. Therefore, Rho is not globally inactivated in Src-transformed fibroblasts, but is necessary for the assembly and function of structures implicated in tumor cell invasion. The Rockefeller University Press 2004-08-02 /pmc/articles/PMC2172255/ /pubmed/15289494 http://dx.doi.org/10.1083/jcb.200312168 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/).
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	Berdeaux, Rebecca L. Díaz, Begoña Kim, Lomi Martin, G. Steven
spellingShingle	Berdeaux, Rebecca L. Díaz, Begoña Kim, Lomi Martin, G. Steven Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function
author_facet	Berdeaux, Rebecca L. Díaz, Begoña Kim, Lomi Martin, G. Steven
author_sort	Berdeaux, Rebecca L.
title	Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function
title_short	Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function
title_full	Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function
title_fullStr	Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function
title_full_unstemmed	Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function
title_sort	active rho is localized to podosomes induced by oncogenic src and is required for their assembly and function
description	Transformation of fibroblasts by oncogenic Src causes disruption of actin stress fibers and formation of invasive adhesions called podosomes. Because the small GTPase Rho stimulates stress fiber formation, Rho inactivation by Src has been thought to be necessary for stress fiber disruption. However, we show here that Rho[GTP] levels do not decrease after transformation by activated Src. Inactivation of Rho in Src-transformed fibroblasts by dominant negative RhoA or the Rho-specific inhibitor C3 exoenzyme disrupted podosome structure as judged by localization of podosome components F-actin, cortactin, and Fish. Inhibition of Rho strongly inhibited Src-induced proteolytic degradation of the extracellular matrix. Furthermore, development of an in situ Rho[GTP] affinity assay allowed us to detect endogenous Rho[GTP] at podosomes, where it colocalized with F-actin, cortactin, and Fish. Therefore, Rho is not globally inactivated in Src-transformed fibroblasts, but is necessary for the assembly and function of structures implicated in tumor cell invasion.
publisher	The Rockefeller University Press
publishDate	2004
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172255/
_version_	1611424864912015360

Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function

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