The small GTPases Ras and Rap1 bind to and control TORC2 activity
Chavan, Anita J.
Montaño, Nieves M.
Briggs, Steven P.
Van Haastert, Peter J. M.
Charest, Pascale G.
AffiliationUniv Arizona, Dept Chem & Biochem
MetadataShow full item record
PublisherNATURE PUBLISHING GROUP
CitationThe small GTPases Ras and Rap1 bind to and control TORC2 activity 2016, 6:25823 Scientific Reports
RightsCopyright © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License.
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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.
VersionFinal published version
SponsorsThe 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.
Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License.