Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control

Robbie Loewith; Estela Jacinto; Stephan Wullschleger; Anja Lorberg; José L Crespo; Débora Bonenfant; Wolfgang Oppliger; Paul Jenoe; Michael N Hall

doi:10.1016/s1097-2765(02)00636-6

Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control

Mol Cell. 2002 Sep;10(3):457-68. doi: 10.1016/s1097-2765(02)00636-6.

Authors

Robbie Loewith¹, Estela Jacinto, Stephan Wullschleger, Anja Lorberg, José L Crespo, Débora Bonenfant, Wolfgang Oppliger, Paul Jenoe, Michael N Hall

Affiliation

¹ Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.

PMID: 12408816
DOI: 10.1016/s1097-2765(02)00636-6

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / metabolism
Animals
Antifungal Agents / pharmacology
Cell Cycle Proteins
Cell Line
Cytoskeleton / metabolism
Drug Resistance, Fungal
Fungal Proteins / genetics
Fungal Proteins / isolation & purification
Fungal Proteins / metabolism*
Genes, Reporter
Glycogen / metabolism
Humans
Macromolecular Substances
Phosphatidylinositol 3-Kinases*
Phosphotransferases (Alcohol Group Acceptor) / genetics
Phosphotransferases (Alcohol Group Acceptor) / isolation & purification
Phosphotransferases (Alcohol Group Acceptor) / metabolism*
Protein Binding
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Saccharomyces cerevisiae / drug effects
Saccharomyces cerevisiae / growth & development*
Saccharomyces cerevisiae / physiology
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / isolation & purification
Saccharomyces cerevisiae Proteins / metabolism
Signal Transduction / physiology
Sirolimus / pharmacology*
Tacrolimus Binding Proteins / genetics
Tacrolimus Binding Proteins / metabolism
Tissue Distribution

Substances

Actins
Antifungal Agents
Cell Cycle Proteins
Fungal Proteins
Macromolecular Substances
Recombinant Fusion Proteins
Saccharomyces cerevisiae Proteins
Glycogen
Phosphotransferases (Alcohol Group Acceptor)
TOR1 protein, S cerevisiae
TOR2 protein, S cerevisiae
Tacrolimus Binding Proteins
Sirolimus