TOR kinase domains are required for two distinct functions, only one of which is inhibited by rapamycin

Cell. 1995 Jul 14;82(1):121-30. doi: 10.1016/0092-8674(95)90058-6.

Abstract

The rapamycin-sensitive signaling pathway is required to transduce specific mitogenic signals to the cell cycle machinery responsible for G1 progression. Genetic studies in yeast identified two related genes on this pathway, TOR1 and TOR2, thought to encode novel phosphatidylinositol kinases. We now show that an intact kinase domain is required for the G1 cell cycle functions of both proteins, for the ability of a mutation in a neighboring FKBP12-rapamycin-binding domain of the TOR1 protein to inhibit the growth of yeast cells when overexpressed, and for the essential function of the TOR2 protein. The G1 function of both TOR proteins is sensitive to rapamycin, but the essential function of TOR2 is not. Thus, FKBP12-rapamycin does not appear to inhibit the kinase activity of TOR proteins in a general way; instead, it may interfere selectively with TOR protein binding to or phosphorylation of G1 effectors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Base Sequence
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins
  • DNA-Binding Proteins / metabolism
  • Drug Resistance, Microbial
  • Fungal Proteins / antagonists & inhibitors
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • G1 Phase / physiology
  • Genes, Fungal
  • Heat-Shock Proteins / metabolism
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases*
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Point Mutation / physiology
  • Polyenes / pharmacology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Sequence Deletion / physiology
  • Signal Transduction / genetics
  • Sirolimus
  • Tacrolimus Binding Proteins

Substances

  • Antifungal Agents
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Fungal Proteins
  • Heat-Shock Proteins
  • Polyenes
  • Saccharomyces cerevisiae Proteins
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • TOR1 protein, S cerevisiae
  • TOR2 protein, S cerevisiae
  • Tacrolimus Binding Proteins
  • Sirolimus