The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration
Cell migration involves the localized extension of actinrich protrusions, a process that requires Class I phosphoinositide 3-kinases (PI 3-kinases). Both Rac and Ras have been shown to regulate actin polymerization and activate PI 3-kinase. However, the coordination of Rac, Ras and PI 3-kinase activ...
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| Format: | article |
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2007
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| Online Access: | http://hdl.handle.net/10725/2493 http://dx.doi.org/10.1242/jcs.005298 http://jcs.biologists.org/content/120/17/3138.short |
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| _version_ | 1864513458280595456 |
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| author | Yip, Shu-Chin |
| author2 | El-Sibai, Mirvat Coniglio, Salvatore J. Mouneimne, Ghassan Eddy, Robert J. Drees, Beth E. Neilsen, Paul O. Goswami, Sumanta Symons, Marc Condeelis, John S. Backer, Jonathan M. |
| author2_role | author author author author author author author author author author |
| author_facet | Yip, Shu-Chin El-Sibai, Mirvat Coniglio, Salvatore J. Mouneimne, Ghassan Eddy, Robert J. Drees, Beth E. Neilsen, Paul O. Goswami, Sumanta Symons, Marc Condeelis, John S. Backer, Jonathan M. |
| author_role | author |
| dc.creator.none.fl_str_mv | Yip, Shu-Chin El-Sibai, Mirvat Coniglio, Salvatore J. Mouneimne, Ghassan Eddy, Robert J. Drees, Beth E. Neilsen, Paul O. Goswami, Sumanta Symons, Marc Condeelis, John S. Backer, Jonathan M. |
| dc.date.none.fl_str_mv | 2007-06-18 2015-11-09T10:22:24Z 2015-11-09T10:22:24Z 2015-11-09 |
| dc.identifier.none.fl_str_mv | 0021-9533 http://hdl.handle.net/10725/2493 http://dx.doi.org/10.1242/jcs.005298 Yip, S. C., El-Sibai, M., Coniglio, S. J., Mouneimne, G., Eddy, R. J., Drees, B. E., ... & Backer, J. M. (2007). The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration. Journal of cell science, 120(17), 3138-3146. http://jcs.biologists.org/content/120/17/3138.short |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Journal of Cell Science |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Cell migration involves the localized extension of actinrich protrusions, a process that requires Class I phosphoinositide 3-kinases (PI 3-kinases). Both Rac and Ras have been shown to regulate actin polymerization and activate PI 3-kinase. However, the coordination of Rac, Ras and PI 3-kinase activation during epidermal growth factor (EGF)-stimulated protrusion has not been analyzed. We examined PI 3-kinase-dependent protrusion in MTLn3 rat adenocarcinoma cells. EGF-stimulated phosphatidy l - inositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] levels showed a rapid and persistent response, as PI 3-kinase activity remained elevated up to 3 minutes. The activation kinetics of Ras, but not Rac, coincided with those of leading-edge PtdIns(3,4,5)P3 production. Small interfering RNA (siRNA) knockdown of K-Ras but not Rac1 abolished PtdIns(3,4,5)P3 production at the leading edge and inhibited EGF-stimulated protrusion. However, Rac1 knockdown did inhibit cell migration, because of the inhibition of focal adhesion formation in Rac1 siRNAtreated cells. Our data show that in EGF-stimulated MTLn3 carcinoma cells, Ras is required for both PtdIns(3,4,5)P3 production and lamellipod extension, whereas Rac1 is required for formation of adhesive structures. These data suggest an unappreciated role for Ras during protrusion, and a crucial role for Rac in the stabilization of protrusions required for cell motility. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_bc8dc816d9fb8a134194c736d7293ac6 |
| identifier_str_mv | 0021-9533 Yip, S. C., El-Sibai, M., Coniglio, S. J., Mouneimne, G., Eddy, R. J., Drees, B. E., ... & Backer, J. M. (2007). The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration. Journal of cell science, 120(17), 3138-3146. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/2493 |
| publishDate | 2007 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migrationYip, Shu-ChinEl-Sibai, MirvatConiglio, Salvatore J.Mouneimne, GhassanEddy, Robert J.Drees, Beth E.Neilsen, Paul O.Goswami, SumantaSymons, MarcCondeelis, John S.Backer, Jonathan M.Cell migration involves the localized extension of actinrich protrusions, a process that requires Class I phosphoinositide 3-kinases (PI 3-kinases). Both Rac and Ras have been shown to regulate actin polymerization and activate PI 3-kinase. However, the coordination of Rac, Ras and PI 3-kinase activation during epidermal growth factor (EGF)-stimulated protrusion has not been analyzed. We examined PI 3-kinase-dependent protrusion in MTLn3 rat adenocarcinoma cells. EGF-stimulated phosphatidy l - inositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] levels showed a rapid and persistent response, as PI 3-kinase activity remained elevated up to 3 minutes. The activation kinetics of Ras, but not Rac, coincided with those of leading-edge PtdIns(3,4,5)P3 production. Small interfering RNA (siRNA) knockdown of K-Ras but not Rac1 abolished PtdIns(3,4,5)P3 production at the leading edge and inhibited EGF-stimulated protrusion. However, Rac1 knockdown did inhibit cell migration, because of the inhibition of focal adhesion formation in Rac1 siRNAtreated cells. Our data show that in EGF-stimulated MTLn3 carcinoma cells, Ras is required for both PtdIns(3,4,5)P3 production and lamellipod extension, whereas Rac1 is required for formation of adhesive structures. These data suggest an unappreciated role for Ras during protrusion, and a crucial role for Rac in the stabilization of protrusions required for cell motility.PublishedN/A2015-11-09T10:22:24Z2015-11-09T10:22:24Z2007-06-182015-11-09Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article0021-9533http://hdl.handle.net/10725/2493http://dx.doi.org/10.1242/jcs.005298Yip, S. C., El-Sibai, M., Coniglio, S. J., Mouneimne, G., Eddy, R. J., Drees, B. E., ... & Backer, J. M. (2007). The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration. Journal of cell science, 120(17), 3138-3146.http://jcs.biologists.org/content/120/17/3138.shortenJournal of Cell Scienceinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/24932020-05-07T23:14:05Z |
| spellingShingle | The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration Yip, Shu-Chin |
| status_str | publishedVersion |
| title | The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration |
| title_full | The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration |
| title_fullStr | The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration |
| title_full_unstemmed | The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration |
| title_short | The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration |
| title_sort | The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration |
| url | http://hdl.handle.net/10725/2493 http://dx.doi.org/10.1242/jcs.005298 http://jcs.biologists.org/content/120/17/3138.short |