Abstract Ras GTPases are ubiquitous plasma membrane transducers of extracellular stimuli. In addition to their role as oncogenes, Ras GTPases are key regulators of cell function. Each of the Ras isoforms exhibits specific modulatory activity on different cellular pathways. This has prompted researchers to determine the pathophysiological roles of each isoform. There is a proven relationship between the signaling pathways of transforming growth factor-β1 (TGF-β1) and Ras GTPases. To assess the individual role of H-Ras oncogene in basal and TGF-β1-mediated extracellular matrix (ECM) synthesis, proliferation, and migration in fibroblasts, we analyzed these processes in embryonic fibroblasts obtained from H-Ras knockout mice ( H-ras −/− ). We found that H- ras −/− fibroblasts exhibited a higher basal phosphatidylinositol-3-kinase (PI3K)/Akt activation than wild-type (WT) fibroblasts, whereas MEK/ERK 1/2 activation was similar in both types of cells. Fibronectin and collagen synthesis were higher in H -ras −/− fibroblasts and proliferation was lower in H -ras −/− than in WT fibroblasts. Moreover, H-Ras appeared indispensable to maintain normal fibroblast motility, which was highly restricted in H- ras −/− cells. These results suggest that H-Ras (through downregulation of PI3K/Akt activation) could modulate fibroblast activity by reducing ECM synthesis and upregulating both proliferation and migration. TGF-β1 strongly increased ERK and Akt activation in WT but not in H- ras −/− fibroblasts, suggesting that H-Ras is necessary to increase ERK 1/2 activation and to maintain PI3K downregulation in TGF-β1-stimulated fibroblasts. TGF-β1 stimulated ECM synthesis and proliferation, although ECM synthesis was higher and proliferation lower in H- ras −/− than in WT fibroblasts. Hence, H-Ras activation seems to play a key role in the regulation of these effects. Ras proteins fibroblast proliferation fibroblast migration transforming growth factor-β1 oncogene Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print November 2011 , doi: 10.​1152/​ajpcell.​00103.​2011 Am J Physiol Cell Physiol February 2012 vol. 302 no. 4 C686-C697 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpcell.00103.2011v1 302/4/C686 most recent Classifications Extracellular Matrix, Cell Interactions Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Fuentes-Calvo, I. Articles by Martínez-Salgado, C. PubMed PubMed citation Articles by Fuentes-Calvo, I. Articles by Martínez-Salgado, C. Related Content Load related web page information Current Issue February 2012, 302 (4) Alert me to new issues of Am J Physiol Cell Physiol About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6143 Online ISSN: 1522-1563 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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