The small GTPases Ras and Rap1 bind to and control TORC2 activity

Persistent Link:
http://hdl.handle.net/10150/614747
Title:
The small GTPases Ras and Rap1 bind to and control TORC2 activity
Author:
Khanna, Ankita; Lotfi, Pouya; Chavan, Anita J.; Montaño, Nieves M.; Bolourani, Parvin; Weeks, Gerald; Shen, Zhouxin; Briggs, Steven P.; Pots, Henderikus; Van Haastert, Peter J. M.; Kortholt, Arjan; Charest, Pascale G.
Affiliation:
Univ Arizona, Dept Chem & Biochem
Issue Date:
2016-05-13
Publisher:
NATURE PUBLISHING GROUP
Citation:
The small GTPases Ras and Rap1 bind to and control TORC2 activity 2016, 6:25823 Scientific Reports
Journal:
Scientific Reports
Rights:
This work is licensed under a Creative Commons Attribution 4.0 International License.
Collection Information:
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
Abstract:
Target of Rapamycin Complex 2 (TORC2) has conserved roles in regulating cytoskeleton dynamics and cell migration and has been linked to cancer metastasis. However, little is known about the mechanisms regulating TORC2 activity and function in any system. In Dictyostelium, TORC2 functions at the front of migrating cells downstream of the Ras protein RasC, controlling F-actin dynamics and cAMP production. Here, we report the identification of the small GTPase Rap1 as a conserved binding partner of the TORC2 component RIP3/SIN1, and that Rap1 positively regulates the RasC-mediated activation of TORC2 in Dictyostelium. Moreover, we show that active RasC binds to the catalytic domain of TOR, suggesting a mechanism of TORC2 activation that is similar to Rheb activation of TOR complex 1. Dual Ras/Rap1 regulation of TORC2 may allow for integration of Ras and Rap1 signaling pathways in directed cell migration.
ISSN:
2045-2322
DOI:
10.1038/srep25823
Keywords:
CONTROLS CELL-ADHESION; DICTYOSTELIUM-DISCOIDEUM; SIGNAL RELAY; MACROPHAGES PROMOTE; MEDIATED ACTIVATION; ACTIN CYTOSKELETON; PARACRINE LOOP; G-PROTEINS; CHEMOTAXIS; MIGRATION
Version:
Final published version
Sponsors:
The authors acknowledge Valery Thompson for technical support, Alfred Wittinghofer for supplying human Rap1b expression plasmid, and Rick Firtel for constructive discussions and critical reading of the manuscript. The work was supported in part by a Research Scholar Grant RSG-15-024-01 - CSM from the American Cancer Society to PGC, by a VIDI-grant of NWO to AK, by a Canadian Institutes of Health Research grant to GW, and a U.S. Public Health Service grant GM037830.
Additional Links:
http://www.nature.com/articles/srep25823

Full metadata record

DC FieldValue Language
dc.contributor.authorKhanna, Ankitaen
dc.contributor.authorLotfi, Pouyaen
dc.contributor.authorChavan, Anita J.en
dc.contributor.authorMontaño, Nieves M.en
dc.contributor.authorBolourani, Parvinen
dc.contributor.authorWeeks, Geralden
dc.contributor.authorShen, Zhouxinen
dc.contributor.authorBriggs, Steven P.en
dc.contributor.authorPots, Henderikusen
dc.contributor.authorVan Haastert, Peter J. M.en
dc.contributor.authorKortholt, Arjanen
dc.contributor.authorCharest, Pascale G.en
dc.date.accessioned2016-06-24T23:36:07Z-
dc.date.available2016-06-24T23:36:07Z-
dc.date.issued2016-05-13-
dc.identifier.citationThe small GTPases Ras and Rap1 bind to and control TORC2 activity 2016, 6:25823 Scientific Reportsen
dc.identifier.issn2045-2322-
dc.identifier.doi10.1038/srep25823-
dc.identifier.urihttp://hdl.handle.net/10150/614747-
dc.description.abstractTarget of Rapamycin Complex 2 (TORC2) has conserved roles in regulating cytoskeleton dynamics and cell migration and has been linked to cancer metastasis. However, little is known about the mechanisms regulating TORC2 activity and function in any system. In Dictyostelium, TORC2 functions at the front of migrating cells downstream of the Ras protein RasC, controlling F-actin dynamics and cAMP production. Here, we report the identification of the small GTPase Rap1 as a conserved binding partner of the TORC2 component RIP3/SIN1, and that Rap1 positively regulates the RasC-mediated activation of TORC2 in Dictyostelium. Moreover, we show that active RasC binds to the catalytic domain of TOR, suggesting a mechanism of TORC2 activation that is similar to Rheb activation of TOR complex 1. Dual Ras/Rap1 regulation of TORC2 may allow for integration of Ras and Rap1 signaling pathways in directed cell migration.en
dc.description.sponsorshipThe authors acknowledge Valery Thompson for technical support, Alfred Wittinghofer for supplying human Rap1b expression plasmid, and Rick Firtel for constructive discussions and critical reading of the manuscript. The work was supported in part by a Research Scholar Grant RSG-15-024-01 - CSM from the American Cancer Society to PGC, by a VIDI-grant of NWO to AK, by a Canadian Institutes of Health Research grant to GW, and a U.S. Public Health Service grant GM037830.en
dc.language.isoenen
dc.publisherNATURE PUBLISHING GROUPen
dc.relation.urlhttp://www.nature.com/articles/srep25823en
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License.en
dc.subjectCONTROLS CELL-ADHESIONen
dc.subjectDICTYOSTELIUM-DISCOIDEUMen
dc.subjectSIGNAL RELAYen
dc.subjectMACROPHAGES PROMOTEen
dc.subjectMEDIATED ACTIVATIONen
dc.subjectACTIN CYTOSKELETONen
dc.subjectPARACRINE LOOPen
dc.subjectG-PROTEINSen
dc.subjectCHEMOTAXISen
dc.subjectMIGRATIONen
dc.titleThe small GTPases Ras and Rap1 bind to and control TORC2 activityen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Dept Chem & Biochemen
dc.identifier.journalScientific Reportsen
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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