title: The small GTPases Ras and Rap1 bind to and control TORC2 activity.
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.
authors.affiliation: Department of Cell Biochemistry, University of Groningen, Groningen, 9747AG, Netherlands.
authors.forename: Ankita
authors.initials: A
authors.lastname: Khanna
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721-0088, USA.
authors.forename: Pouya
authors.initials: P
authors.lastname: Lotfi
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721-0088, USA.
authors.forename: Anita J
authors.initials: AJ
authors.lastname: Chavan
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721-0088, USA.
authors.forename: Nieves M
authors.initials: NM
authors.lastname: Montaño
authors.affiliation: Department of Microbiology and Immunology, Life Sciences Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Parvin
authors.initials: P
authors.lastname: Bolourani
authors.affiliation: Department of Microbiology and Immunology, Life Sciences Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Gerald
authors.initials: G
authors.lastname: Weeks
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093-0380, USA.
authors.forename: Zhouxin
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093-0380, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Briggs
authors.affiliation: Department of Cell Biochemistry, University of Groningen, Groningen, 9747AG, Netherlands.
authors.forename: Henderikus
authors.initials: H
authors.lastname: Pots
authors.affiliation: Department of Cell Biochemistry, University of Groningen, Groningen, 9747AG, Netherlands.
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Van Haastert
authors.affiliation: Department of Cell Biochemistry, University of Groningen, Groningen, 9747AG, Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Kortholt
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721-0088, USA.
authors.forename: Pascale G
authors.initials: PG
authors.lastname: Charest
mesh_terms: D017124:Conserved Sequence; D004023:Dictyostelium / Q000378:metabolism*; D000076225:Mechanistic Target of Rapamycin Complex 2 / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D000076225:Mechanistic Target of Rapamycin Complex 2; D020827:rap1 GTP-Binding Proteins; D018631:ras Proteins