Mammalian target of rapamycin: immunosuppressive drugs uncover a novel pathway of cytokine receptor signaling.
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.
Abraham
R T
RT
Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA. abraham.robert@mayo.edu
D064413:3-Phosphoinositide-Dependent Protein Kinases; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000502:physiology; D004789:Enzyme Activation; D039642:Eukaryotic Initiation Factors; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006360:Heat-Shock Proteins / Q000187:drug effects* / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D018448:Models, Immunological; D005810:Multigene Family; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000502:physiology; D011090:Polyenes / Q000494:pharmacology*; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins
D064413:3-Phosphoinositide-Dependent Protein Kinases; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D039642:Eukaryotic Initiation Factors; D005656:Fungal Proteins; D006133:Growth Substances; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D011090:Polyenes; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D016559:Tacrolimus; D022021:Tacrolimus Binding Proteins; C087000:EIF4EBP1 protein, human; C499527:Eif4ebp1 protein, mouse; C546842:MTOR protein, human; C546843:mTOR protein, mouse; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae