Mammalian target of rapamycin: immunosuppressive drugs uncover a novel pathway of cytokine receptor signaling

Curr Opin Immunol. 1998 Jun;10(3):330-6. doi: 10.1016/s0952-7915(98)80172-6.

Abstract

Recent findings have significantly advanced our understanding of the mechanism by which the potent immunosuppressive drug rapamycin inhibits cytokine-dependent lymphocyte proliferation. The protein targeted by the immunophilin-rapamycin complex is a member of a newly defined family of phosphoinositide-3-kinase-related kinases. The rapamycin target protein functions as a protein kinase in a signal transduction pathway that regulates the synthesis of proteins required for cell-cycle progression in both lymphoid and nonlymphoid cells.

Publication types

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

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Carrier Proteins / drug effects*
  • Carrier Proteins / physiology
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / genetics
  • Cell Survival
  • DNA-Binding Proteins / drug effects*
  • DNA-Binding Proteins / physiology
  • Enzyme Activation
  • Eukaryotic Initiation Factors
  • Fungal Proteins / genetics
  • Fungal Proteins / physiology
  • Gene Expression Regulation / physiology
  • Growth Substances / physiology
  • Heat-Shock Proteins / drug effects*
  • Heat-Shock Proteins / physiology
  • Immunosuppressive Agents / pharmacology*
  • Mice
  • Models, Immunological
  • Multigene Family
  • Phosphatidylinositol 3-Kinases*
  • Phosphoproteins / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / physiology
  • Polyenes / pharmacology*
  • Protein Kinases*
  • Protein-Serine-Threonine Kinases / chemistry
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction / physiology*
  • Sirolimus
  • TOR Serine-Threonine Kinases
  • Tacrolimus / pharmacology
  • Tacrolimus Binding Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • EIF4EBP1 protein, human
  • Eif4ebp1 protein, mouse
  • Eukaryotic Initiation Factors
  • Fungal Proteins
  • Growth Substances
  • Heat-Shock Proteins
  • Immunosuppressive Agents
  • Phosphoproteins
  • Polyenes
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • TOR1 protein, S cerevisiae
  • TOR2 protein, S cerevisiae
  • 3-Phosphoinositide-Dependent Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Tacrolimus Binding Proteins
  • Sirolimus
  • Tacrolimus