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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| Veröffentlicht in: | The Journal of cell biology 2004-08, Vol.166 (3), p.317-323 |
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| container_title | The Journal of cell biology |
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| creator | Berdeaux, Rebecca L. Díaz, Begoña Kim, Lomi Martin, G. Steven |
| 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. |
| doi_str_mv | 10.1083/jcb.200312168 |
| format | Article |
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Steven</creator><creatorcontrib>Berdeaux, Rebecca L. ; Díaz, Begoña ; Kim, Lomi ; Martin, G. Steven</creatorcontrib><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.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.200312168</identifier><identifier>PMID: 15289494</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Actins ; Actins - metabolism ; Animals ; Cells ; Cellular biology ; Dendritic cells ; Endothelial cells ; Fibroblasts ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Focal adhesions ; Gelatins ; Genes ; Humans ; Microscopy, Fluorescence ; Physiological regulation ; Proteins ; rho GTP-Binding Proteins - metabolism ; Secretion ; src-Family Kinases - metabolism ; Stress fibers</subject><ispartof>The Journal of cell biology, 2004-08, Vol.166 (3), p.317-323</ispartof><rights>Copyright 2004 The Rockefeller University Press</rights><rights>Copyright Rockefeller University Press Aug 2, 2004</rights><rights>Copyright © 2004, The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-94dab236faa2ff8696e6fe99f756c86078ab5fd15838208e24d0ef75cf2f9eed3</citedby><cites>FETCH-LOGICAL-c495t-94dab236faa2ff8696e6fe99f756c86078ab5fd15838208e24d0ef75cf2f9eed3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15289494$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Berdeaux, Rebecca L.</creatorcontrib><creatorcontrib>Díaz, Begoña</creatorcontrib><creatorcontrib>Kim, Lomi</creatorcontrib><creatorcontrib>Martin, G. Steven</creatorcontrib><title>Active Rho Is Localized to Podosomes Induced by Oncogenic Src and Is Required for Their Assembly and Function</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><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.</description><subject>Actins</subject><subject>Actins - metabolism</subject><subject>Animals</subject><subject>Cells</subject><subject>Cellular biology</subject><subject>Dendritic cells</subject><subject>Endothelial cells</subject><subject>Fibroblasts</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Focal adhesions</subject><subject>Gelatins</subject><subject>Genes</subject><subject>Humans</subject><subject>Microscopy, Fluorescence</subject><subject>Physiological regulation</subject><subject>Proteins</subject><subject>rho GTP-Binding Proteins - metabolism</subject><subject>Secretion</subject><subject>src-Family Kinases - metabolism</subject><subject>Stress fibers</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFksFvFCEYxYmxsevq0ZsxxIPxMhUYYODSZNNY3WSTmlrPhGE-urOZGVqYabL-9bLupq09VC4kvB_vg5eH0DtKTihR5ZeNq08YISVlVKoXaEYFJ4WinLxEM0IYLbRg4hi9TmlDCOEVL1-hYyqY0lzzGeoXbmzvAF-uA14mvArOdu1vaPAY8I_QhBR6SHg5NJPLh_UWXwwuXMPQOvwzOmyHZnftEm6nNmbAh4iv1tBGvEgJ-rrb_kXOpyGPCcMbdORtl-DtYZ-jX-dfr86-F6uLb8uzxapwXIux0LyxNSult5Z5r6SWID1o7SshnZKkUrYWvqFClYoRBYw3BLLoPPMaoCnn6HTvezPVPTQOhjHaztzEtrdxa4Jtzb_K0K7NdbgzjFaMCZENPh0MYridII2mb5ODrrMDhCkZKSvJdM5_jj4_C1JVCcUFI_K_nrSSSlO9G_7xCbgJUxxyYLv3kTxWsgwVe8jFkFIEf_87SsyuGSY3w9w3I_MfHkfyQB-qkIH3e2CTxhAfdMlYmdcf1Ka9rg</recordid><startdate>20040802</startdate><enddate>20040802</enddate><creator>Berdeaux, Rebecca L.</creator><creator>Díaz, Begoña</creator><creator>Kim, Lomi</creator><creator>Martin, G. 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Steven</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-94dab236faa2ff8696e6fe99f756c86078ab5fd15838208e24d0ef75cf2f9eed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Actins</topic><topic>Actins - metabolism</topic><topic>Animals</topic><topic>Cells</topic><topic>Cellular biology</topic><topic>Dendritic cells</topic><topic>Endothelial cells</topic><topic>Fibroblasts</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - metabolism</topic><topic>Focal adhesions</topic><topic>Gelatins</topic><topic>Genes</topic><topic>Humans</topic><topic>Microscopy, Fluorescence</topic><topic>Physiological regulation</topic><topic>Proteins</topic><topic>rho GTP-Binding Proteins - metabolism</topic><topic>Secretion</topic><topic>src-Family Kinases - metabolism</topic><topic>Stress fibers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Berdeaux, Rebecca L.</creatorcontrib><creatorcontrib>Díaz, Begoña</creatorcontrib><creatorcontrib>Kim, Lomi</creatorcontrib><creatorcontrib>Martin, G. 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Steven</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Active Rho Is Localized to Podosomes Induced by Oncogenic Src and Is Required for Their Assembly and Function</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2004-08-02</date><risdate>2004</risdate><volume>166</volume><issue>3</issue><spage>317</spage><epage>323</epage><pages>317-323</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><coden>JCLBA3</coden><abstract>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.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>15289494</pmid><doi>10.1083/jcb.200312168</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Actins Actins - metabolism Animals Cells Cellular biology Dendritic cells Endothelial cells Fibroblasts Fibroblasts - cytology Fibroblasts - metabolism Focal adhesions Gelatins Genes Humans Microscopy, Fluorescence Physiological regulation Proteins rho GTP-Binding Proteins - metabolism Secretion src-Family Kinases - metabolism Stress fibers |
| title | Active Rho Is Localized to Podosomes Induced by Oncogenic Src and Is Required for Their Assembly and Function |
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