IMMUNOPHARMACOLOGY OF RAPAMYCIN

Annual Review of Immunology - Tập 14 Số 1 - Trang 483-510 - 1996
Robert T. Abraham1,2, Gregory J. Wiederrecht1,2
1*Department of Immunology, Mayo Clinic/Foundation, Room 342B, Guggenheim Building, Rochester, Minnesota 55905
2Department of Immunology Research, Merck Research Laboratories, PO Box 2000, Mail Code R80W-107, Rahway, New Jersey, 07065

Tóm tắt

▪ Abstract  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 G1into the S phase of the cell cycle. Here we review the immunopharmacology of rapamycin, with particular emphasis on the characterization of mTOR.

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Annual Review of Immunology

Tập 14 Số 1

483-510

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