Immunopharmacology of rapamycin.
The potent immunosuppressive drugs FK506 and rapamycin interfere with signal transduction pathways required for T cell activation and growth. The distinct inhibitory effects of these drugs on the T cell activation program are mediated through the formation of pharmacologically active complexes with members of a family of intracellular receptors termed the FK506 binding proteins (FKBPs). The FKBP12.FK506 complex specifically binds to and inhibits calcineurin, a signaling protein required for transcriptional activation of the interleukin (IL)-2 gene in response to T cell antigen receptor engagement. The FKBP12. rapamycin complex interacts with a recently defined target protein termed the mammalian target of rapamycin (mTOR). Accumulating data suggest that mTOR functions in a previously unrecognized signal transduction pathway required for the progression of IL-2-stimulated T cells from G1 into the S phase of the cell cycle. Here we review the immunopharmacology of rapamycin, with particular emphasis on the characterization of mTOR.
Abraham
R T
RT
Department of Immunology, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.
Wiederrecht
G J
GJ
D000818:Animals; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000494:pharmacology*; D011090:Polyenes / Q000276:immunology* / Q000494:pharmacology*; D020123:Sirolimus
D007166:Immunosuppressive Agents; D011090:Polyenes; D020123:Sirolimus