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 |
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Přispěvatelé: | Cell Biochemistry |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
G protein Protozoan Proteins Mechanistic Target of Rapamycin Complex 2 GTPase Biology Models Biological Article 03 medical and health sciences TOR complex Dictyostelium Small GTPase Phosphorylation chemotaxis Conserved Sequence nutrient signalling Multidisciplinary rap1 GTP-Binding Proteins biology.organism_classification Actin cytoskeleton Cell biology 030104 developmental biology ras Proteins biology.protein Rap1 Protein Binding RHEB |
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 |
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