This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Giannoni, E. Articles by Chiarugi, P. Search for Related Content PubMed PubMed Citation Articles by Giannoni, E. Articles by Chiarugi, P.

Intracellular Reactive Oxygen Species Activate Src Tyrosine Kinase during Cell Adhesion and Anchorage-Dependent Cell Growth

Department of Biochemical Sciences, University of Florence, V.le Morgagni 50, 50134 Florence, Italy,¹ Center for Research, Transfer and High Education, Study at molecular and clinical level of chronic, inflammatory, degenerative and neoplastic disorders for the development of novel therapies, Florence, Italy²

Received 27 December 2004/ Returned for modification 16 February 2005/ Accepted 4 May 2005

Src tyrosine kinases are central components of adhesive responses and are required for cell spreading onto the extracellular matrix. Among other intracellular messengers elicited by integrin ligation are reactive oxygen species, which act as synergistic mediators of cytoskeleton rearrangement and cell spreading. We report that after integrin ligation, the tyrosine kinase Src is oxidized and activated. Src displays an early activation phase, concurrent with focal adhesion formation and driven mainly by Tyr527 dephosphorylation, and a late phase, concomitant with reactive oxygen species production, cell spreading, and integrin-elicited kinase oxidation. In addition, our results suggest that reactive oxygen species are key mediators of in vitro and in vivo v-Src tumorigenic properties, as both antioxidant treatments and the oxidant-insensitive C245A and C487A Src mutants greatly decrease invasivity, serum-independent and anchorage-independent growth, and tumor onset. Therefore we propose that, in addition to the known phosphorylation/dephosphorylation circuitry, redox regulation of Src activity is required during both cell attachment to the extracellular matrix and tumorigenesis.

Supplemental material for this article may be found at http://mcb.asm.org/.

This article has been cited by other articles:

• Song, Y., Driessens, N., Costa, M., De Deken, X., Detours, V., Corvilain, B., Maenhaut, C., Miot, F., Van Sande, J., Many, M.-C., Dumont, J. E. (2007). Roles of Hydrogen Peroxide in Thyroid Physiology and Disease. J. Clin. Endocrinol. Metab. 92: 3764-3773 [Abstract] [Full Text]  
• Sangrar, W., Gao, Y., Scott, M., Truesdell, P., Greer, P. A. (2007). Fer-Mediated Cortactin Phosphorylation Is Associated with Efficient Fibroblast Migration and Is Dependent on Reactive Oxygen Species Generation during Integrin-Mediated Cell Adhesion. Mol. Cell. Biol. 27: 6140-6152 [Abstract] [Full Text]  
• Lluis, J. M., Buricchi, F., Chiarugi, P., Morales, A., Fernandez-Checa, J. C. (2007). Dual Role of Mitochondrial Reactive Oxygen Species in Hypoxia Signaling: Activation of Nuclear Factor-{kappa}B via c-SRC and Oxidant-Dependent Cell Death. Cancer Res. 67: 7368-7377 [Abstract] [Full Text]  
• Wang, P.-X., Sanders, P. W. (2007). Immunoglobulin Light Chains Generate Hydrogen Peroxide. J. Am. Soc. Nephrol. 18: 1239-1245 [Abstract] [Full Text]  
• Forrester, M. T., Stamler, J. S. (2007). A Classification Scheme for Redox-Based Modifications of Proteins. Am. J. Respir. Cell Mol. Bio. 36: 135-137 [Full Text]  
• Fiaschi, T., Cozzi, G., Raugei, G., Formigli, L., Ramponi, G., Chiarugi, P. (2006). Redox Regulation of beta-Actin during Integrin-mediated Cell Adhesion. J. Biol. Chem. 281: 22983-22991 [Abstract] [Full Text]