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.

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
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • TOR1 protein, S cerevisiae
  • TOR2 protein, S cerevisiae
  • Tacrolimus Binding Proteins
  • Sirolimus