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β3 Integrin–EGF receptor cross-talk activates p190RhoGAP in mouse mammary gland epithelial cells
Active RhoA localizes to plasma membrane, where it stimulates formation of focal adhesions and stress fibers. RhoA activity is inhibited by p190RhoGAP following integrin-mediated cell attachment to allow sampling of new adhesive environments. p190RhoGAP is itself activated by Src-dependent tyrosine...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216655/ https://www.ncbi.nlm.nih.gov/pubmed/21937717 http://dx.doi.org/10.1091/mbc.E10-08-0700 |
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author | Balanis, Nikolas Yoshigi, Masaaki Wendt, Michael K. Schiemann, William P. Carlin, Cathleen R. |
author_facet | Balanis, Nikolas Yoshigi, Masaaki Wendt, Michael K. Schiemann, William P. Carlin, Cathleen R. |
author_sort | Balanis, Nikolas |
collection | PubMed |
description | Active RhoA localizes to plasma membrane, where it stimulates formation of focal adhesions and stress fibers. RhoA activity is inhibited by p190RhoGAP following integrin-mediated cell attachment to allow sampling of new adhesive environments. p190RhoGAP is itself activated by Src-dependent tyrosine phosphorylation, which facilitates complex formation with p120RasGAP. This complex then translocates to the cell surface, where p190RhoGAP down-regulates RhoA. Here we demonstrate that the epidermal growth factor receptor (EGFR) cooperates with β3 integrin to regulate p190RhoGAP activity in mouse mammary gland epithelial cells. Adhesion to fibronectin stimulates tyrosine phosphorylation of the EGFR in the absence of receptor ligands. Use of a dominant inhibitory EGFR mutant demonstrates that fibronectin-activated EGFR recruits p120RasGAP to the cell periphery. Expression of an inactive β3 integrin subunit abolishes p190RhoGAP tyrosine phosphorylation, demonstrating a mechanistic link between β3 integrin–activated Src and EGFR regulation of the RhoA inhibitor. The β3 integrin/EGFR pathway also has a positive role in formation of filopodia. Together our data suggest that EGFR constitutes an important intrinsic migratory cue since fibronectin is a key component of the microenvironment in normal mammary gland development and breast cancer. Our data also suggest that EGFR expressed at high levels has a role in eliciting cell shape changes associated with epithelial-to-mesenchymal transition. |
format | Online Article Text |
id | pubmed-3216655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-32166552012-01-30 β3 Integrin–EGF receptor cross-talk activates p190RhoGAP in mouse mammary gland epithelial cells Balanis, Nikolas Yoshigi, Masaaki Wendt, Michael K. Schiemann, William P. Carlin, Cathleen R. Mol Biol Cell Articles Active RhoA localizes to plasma membrane, where it stimulates formation of focal adhesions and stress fibers. RhoA activity is inhibited by p190RhoGAP following integrin-mediated cell attachment to allow sampling of new adhesive environments. p190RhoGAP is itself activated by Src-dependent tyrosine phosphorylation, which facilitates complex formation with p120RasGAP. This complex then translocates to the cell surface, where p190RhoGAP down-regulates RhoA. Here we demonstrate that the epidermal growth factor receptor (EGFR) cooperates with β3 integrin to regulate p190RhoGAP activity in mouse mammary gland epithelial cells. Adhesion to fibronectin stimulates tyrosine phosphorylation of the EGFR in the absence of receptor ligands. Use of a dominant inhibitory EGFR mutant demonstrates that fibronectin-activated EGFR recruits p120RasGAP to the cell periphery. Expression of an inactive β3 integrin subunit abolishes p190RhoGAP tyrosine phosphorylation, demonstrating a mechanistic link between β3 integrin–activated Src and EGFR regulation of the RhoA inhibitor. The β3 integrin/EGFR pathway also has a positive role in formation of filopodia. Together our data suggest that EGFR constitutes an important intrinsic migratory cue since fibronectin is a key component of the microenvironment in normal mammary gland development and breast cancer. Our data also suggest that EGFR expressed at high levels has a role in eliciting cell shape changes associated with epithelial-to-mesenchymal transition. The American Society for Cell Biology 2011-11-15 /pmc/articles/PMC3216655/ /pubmed/21937717 http://dx.doi.org/10.1091/mbc.E10-08-0700 Text en © 2011 Balanis et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Balanis, Nikolas Yoshigi, Masaaki Wendt, Michael K. Schiemann, William P. Carlin, Cathleen R. β3 Integrin–EGF receptor cross-talk activates p190RhoGAP in mouse mammary gland epithelial cells |
title | β3 Integrin–EGF receptor cross-talk activates p190RhoGAP in mouse mammary gland epithelial cells |
title_full | β3 Integrin–EGF receptor cross-talk activates p190RhoGAP in mouse mammary gland epithelial cells |
title_fullStr | β3 Integrin–EGF receptor cross-talk activates p190RhoGAP in mouse mammary gland epithelial cells |
title_full_unstemmed | β3 Integrin–EGF receptor cross-talk activates p190RhoGAP in mouse mammary gland epithelial cells |
title_short | β3 Integrin–EGF receptor cross-talk activates p190RhoGAP in mouse mammary gland epithelial cells |
title_sort | β3 integrin–egf receptor cross-talk activates p190rhogap in mouse mammary gland epithelial cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216655/ https://www.ncbi.nlm.nih.gov/pubmed/21937717 http://dx.doi.org/10.1091/mbc.E10-08-0700 |
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