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

Ankita Khanna, Pouya Lotfi, Anita J. Chavan, Nieves M. Montaño, Parvin Bolourani, Gerald Weeks, Zhouxin Shen, Steven P. Briggs, Henderikus Pots, Peter J M Van Haastert, Arjan Kortholt, Pascale G Charest

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Article number25823
JournalScientific Reports
Volume6
DOIs
StatePublished - May 13 2016

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Monomeric GTP-Binding Proteins
Dictyostelium
Cell Movement
ras Proteins
TOR complex 2
Cytoskeleton
Actins
Catalytic Domain
Neoplasm Metastasis
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Khanna, A., Lotfi, P., Chavan, A. J., Montaño, N. M., Bolourani, P., Weeks, G., ... Charest, P. G. (2016). The small GTPases Ras and Rap1 bind to and control TORC2 activity. Scientific Reports, 6, [25823]. https://doi.org/10.1038/srep25823

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

In: Scientific Reports, Vol. 6, 25823, 13.05.2016.

Research output: Contribution to journalArticle

Khanna, A, Lotfi, P, Chavan, AJ, Montaño, NM, Bolourani, P, Weeks, G, Shen, Z, Briggs, SP, Pots, H, Van Haastert, PJM, Kortholt, A & Charest, PG 2016, 'The small GTPases Ras and Rap1 bind to and control TORC2 activity', Scientific Reports, vol. 6, 25823. https://doi.org/10.1038/srep25823
Khanna A, Lotfi P, Chavan AJ, Montaño NM, Bolourani P, Weeks G et al. The small GTPases Ras and Rap1 bind to and control TORC2 activity. Scientific Reports. 2016 May 13;6. 25823. https://doi.org/10.1038/srep25823
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. / The small GTPases Ras and Rap1 bind to and control TORC2 activity. In: Scientific Reports. 2016 ; Vol. 6.
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