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

Autor: Khanna A; Department of Cell Biochemistry, University of Groningen, Groningen, 9747AG, Netherlands., Lotfi P; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721-0088, USA., Chavan AJ; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721-0088, USA., Montaño NM; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721-0088, USA., Bolourani P; Department of Microbiology and Immunology, Life Sciences Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada., Weeks G; Department of Microbiology and Immunology, Life Sciences Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada., Shen Z; Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093-0380, USA., Briggs SP; Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093-0380, USA., Pots H; Department of Cell Biochemistry, University of Groningen, Groningen, 9747AG, Netherlands., Van Haastert PJ; Department of Cell Biochemistry, University of Groningen, Groningen, 9747AG, Netherlands., Kortholt A; Department of Cell Biochemistry, University of Groningen, Groningen, 9747AG, Netherlands., Charest PG; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721-0088, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2016 May 13; Vol. 6, pp. 25823. Date of Electronic Publication: 2016 May 13.
DOI: 10.1038/srep25823
Abstrakt: 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: MEDLINE