RhoA/ROCK-mediated switching between Cdc42- and Rac1-dependent protrusion in MTLn3 carcinoma cells
Rho GTPases are versatile regulators of cell shape that act on the actin cytoskeleton. Studies using Rho GTPase mutants have shown that, in some cells, Rac1 and Cdc42 regulate the formation of lamellipodia and filopodia, respectively at the leading edge, whereas RhoA mediates contraction at the rear...
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| Format: | article |
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2008
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| Online Access: | http://hdl.handle.net/10725/2440 http://dx.doi.org/10.1016/j.yexcr.2008.01.016 http://www.ncbi.nlm.nih.gov/pubmed/18316075 |
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| _version_ | 1864513458238652416 |
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| author | El-Sibai, Mirvat |
| author2 | Pertz, Olivier Pang, Huan Yip, Shu-Chin Lorenz, Mike Symons, Marc Condeelis, John S. Hahn, Klaus M. Backer, Jonathan M. |
| author2_role | author author author author author author author author |
| author_facet | El-Sibai, Mirvat Pertz, Olivier Pang, Huan Yip, Shu-Chin Lorenz, Mike Symons, Marc Condeelis, John S. Hahn, Klaus M. Backer, Jonathan M. |
| author_role | author |
| dc.creator.none.fl_str_mv | El-Sibai, Mirvat Pertz, Olivier Pang, Huan Yip, Shu-Chin Lorenz, Mike Symons, Marc Condeelis, John S. Hahn, Klaus M. Backer, Jonathan M. |
| dc.date.none.fl_str_mv | 2008-04-15 2015-11-04T13:58:41Z 2015-11-04T13:58:41Z 2015-11-04 |
| dc.identifier.none.fl_str_mv | 0014-4827 http://hdl.handle.net/10725/2440 http://dx.doi.org/10.1016/j.yexcr.2008.01.016 El-Sibai, M., Pertz, O., Pang, H., Yip, S. C., Lorenz, M., Symons, M., ... & Backer, J. M. (2008). RhoA/ROCK-mediated switching between Cdc42-and Rac1-dependent protrusion in MTLn3 carcinoma cells. Experimental cell research, 314(7), 1540-1552. http://www.ncbi.nlm.nih.gov/pubmed/18316075 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Experimental Cell Research |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | RhoA/ROCK-mediated switching between Cdc42- and Rac1-dependent protrusion in MTLn3 carcinoma cells |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Rho GTPases are versatile regulators of cell shape that act on the actin cytoskeleton. Studies using Rho GTPase mutants have shown that, in some cells, Rac1 and Cdc42 regulate the formation of lamellipodia and filopodia, respectively at the leading edge, whereas RhoA mediates contraction at the rear of moving cells. However, recent reports have described a zone of RhoA/ROCK activation at the front of cells undergoing motility. In this study, we use a FRET-based RhoA biosensor to show that RhoA activation localizes to the leading edge of EGF-stimulated cells. Inhibition of Rho or ROCK enhanced protrusion, yet markedly inhibited cell motility; these changes correlated with a marked activation of Rac-1 at the cell edge. Surprisingly, whereas EGF-stimulated protrusion in control MTLn3 cells is Rac-independent and Cdc42-dependent, the opposite pattern is observed in MTLn3 cells after inhibition of ROCK. Thus, Rho and ROCK suppress Rac-1 activation at the leading edge, and inhibition of ROCK causes a switch between Cdc42 and Rac-1 as the dominant Rho GTPase driving protrusion in carcinoma cells. These data describe a novel role for Rho in coordinating signaling by Rac and Cdc42. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_dd526ac6973c544ca6cb0e1bd0e77e8f |
| identifier_str_mv | 0014-4827 El-Sibai, M., Pertz, O., Pang, H., Yip, S. C., Lorenz, M., Symons, M., ... & Backer, J. M. (2008). RhoA/ROCK-mediated switching between Cdc42-and Rac1-dependent protrusion in MTLn3 carcinoma cells. Experimental cell research, 314(7), 1540-1552. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/2440 |
| publishDate | 2008 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | RhoA/ROCK-mediated switching between Cdc42- and Rac1-dependent protrusion in MTLn3 carcinoma cellsEl-Sibai, MirvatPertz, OlivierPang, HuanYip, Shu-ChinLorenz, MikeSymons, MarcCondeelis, John S.Hahn, Klaus M.Backer, Jonathan M.Rho GTPases are versatile regulators of cell shape that act on the actin cytoskeleton. Studies using Rho GTPase mutants have shown that, in some cells, Rac1 and Cdc42 regulate the formation of lamellipodia and filopodia, respectively at the leading edge, whereas RhoA mediates contraction at the rear of moving cells. However, recent reports have described a zone of RhoA/ROCK activation at the front of cells undergoing motility. In this study, we use a FRET-based RhoA biosensor to show that RhoA activation localizes to the leading edge of EGF-stimulated cells. Inhibition of Rho or ROCK enhanced protrusion, yet markedly inhibited cell motility; these changes correlated with a marked activation of Rac-1 at the cell edge. Surprisingly, whereas EGF-stimulated protrusion in control MTLn3 cells is Rac-independent and Cdc42-dependent, the opposite pattern is observed in MTLn3 cells after inhibition of ROCK. Thus, Rho and ROCK suppress Rac-1 activation at the leading edge, and inhibition of ROCK causes a switch between Cdc42 and Rac-1 as the dominant Rho GTPase driving protrusion in carcinoma cells. These data describe a novel role for Rho in coordinating signaling by Rac and Cdc42.PublishedN/A2015-11-04T13:58:41Z2015-11-04T13:58:41Z2008-04-152015-11-04Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article0014-4827http://hdl.handle.net/10725/2440http://dx.doi.org/10.1016/j.yexcr.2008.01.016El-Sibai, M., Pertz, O., Pang, H., Yip, S. C., Lorenz, M., Symons, M., ... & Backer, J. M. (2008). RhoA/ROCK-mediated switching between Cdc42-and Rac1-dependent protrusion in MTLn3 carcinoma cells. Experimental cell research, 314(7), 1540-1552.http://www.ncbi.nlm.nih.gov/pubmed/18316075enExperimental Cell Researchinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/24402020-05-24T09:08:55Z |
| spellingShingle | RhoA/ROCK-mediated switching between Cdc42- and Rac1-dependent protrusion in MTLn3 carcinoma cells El-Sibai, Mirvat |
| status_str | publishedVersion |
| title | RhoA/ROCK-mediated switching between Cdc42- and Rac1-dependent protrusion in MTLn3 carcinoma cells |
| title_full | RhoA/ROCK-mediated switching between Cdc42- and Rac1-dependent protrusion in MTLn3 carcinoma cells |
| title_fullStr | RhoA/ROCK-mediated switching between Cdc42- and Rac1-dependent protrusion in MTLn3 carcinoma cells |
| title_full_unstemmed | RhoA/ROCK-mediated switching between Cdc42- and Rac1-dependent protrusion in MTLn3 carcinoma cells |
| title_short | RhoA/ROCK-mediated switching between Cdc42- and Rac1-dependent protrusion in MTLn3 carcinoma cells |
| title_sort | RhoA/ROCK-mediated switching between Cdc42- and Rac1-dependent protrusion in MTLn3 carcinoma cells |
| url | http://hdl.handle.net/10725/2440 http://dx.doi.org/10.1016/j.yexcr.2008.01.016 http://www.ncbi.nlm.nih.gov/pubmed/18316075 |