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

Autor: Steven P. Briggs, Gerald Weeks, Arjan Kortholt, Peter J.M. van Haastert, Nieves M Montaño, Pouya Lotfi, Zhouxin Shen, Henderikus Pots, Parvin Bolourani, Anita J Chavan, Pascale G. Charest, Ankita Khanna
Přispěvatelé: Cell Biochemistry
Rok vydání: 2016
Předmět:
Zdroj: Scientific Reports, 6:25823, 1-9. Nature Publishing Group
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/srep25823
Popis: 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.
Databáze: OpenAIRE