IMMUNOPHARMACOLOGY OF RAPAMYCIN
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.
Từ khóa
Tài liệu tham khảo
Morris RE, 1989, Med. Sci. Res., 17, 609
Eng CP, 1991, Transplant. Proc., 23, 868
Morris RE, 1990, Transplant. Proc., 22, 1638
Collier DSJ, 1990, Transplant. Proc., 22, 1674
Collier DSJ, 1991, Transplant. Proc., 23, 2246
Morris RE, 1991, Transplant. Proc., 23, 521
Collier DSJ, 1988, Transplant. Proc., 20, S226
Ryffel B, 1986, Prog. Allergy., 39, 181
Shapiro R, 1990, Transplant. Proc., 22, 35
Groth C-G, 1993, Transplant. Proc., 25, 2681
Borman S, 1994, C & EN July 4,
Dumont F, 1994, J. Pharmacol. Exp. Ther:, 268, 32
Barbet N, 1995, Mol. Biol. Cell
Sonenberg N, 1993, Gene Exp., 3, 317
Murray A, 1994, Curr. Opin. Cell Biol., 79, 551