title: Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control.
abstract: The target of rapamycin (TOR) proteins in Saccharomyces cerevisiae, TOR1 and TOR2, redundantly regulate growth in a rapamycin-sensitive manner. TOR2 additionally regulates polarization of the actin cytoskeleton in a rapamycin-insensitive manner. We describe two functionally distinct TOR complexes. TOR Complex 1 (TORC1) contains TOR1 or TOR2, KOG1 (YHR186c), and LST8. TORC2 contains TOR2, AVO1 (YOL078w), AVO2 (YMR068w), AVO3 (YER093c), and LST8. FKBP-rapamycin binds TORC1, and TORC1 disruption mimics rapamycin treatment, suggesting that TORC1 mediates the rapamycin-sensitive, TOR-shared pathway. FKBP-rapamycin fails to bind TORC2, and TORC2 disruption causes an actin defect, suggesting that TORC2 mediates the rapamycin-insensitive, TOR2-unique pathway. Thus, the distinct TOR complexes account for the diversity, specificity, and selective rapamycin inhibition of TOR signaling. TORC1 and possibly TORC2 are conserved from yeast to man.
authors.affiliation: Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
authors.forename: Robbie
authors.initials: R
authors.lastname: Loewith
authors.forename: Estela
authors.initials: E
authors.lastname: Jacinto
authors.forename: Stephan
authors.initials: S
authors.lastname: Wullschleger
authors.forename: Anja
authors.initials: A
authors.lastname: Lorberg
authors.forename: José L
authors.initials: JL
authors.lastname: Crespo
authors.forename: Débora
authors.initials: D
authors.lastname: Bonenfant
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Oppliger
authors.forename: Paul
authors.initials: P
authors.lastname: Jenoe
authors.forename: Michael N
authors.initials: MN
authors.lastname: Hall
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D018797:Cell Cycle Proteins; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017930:Genes, Reporter; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000199:Actins; D000935:Antifungal Agents; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D006003:Glycogen; D046911:Macromolecular Substances; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; D022021:Tacrolimus Binding Proteins; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae