Abraham R T, Wiederrecht G J
Department of Immunology, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.
Annu Rev Immunol. 1996;14:483-510. doi: 10.1146/annurev.immunol.14.1.483.
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.
强效免疫抑制药物FK506和雷帕霉素会干扰T细胞活化和生长所需的信号转导途径。这些药物对T细胞活化程序的独特抑制作用是通过与一类称为FK506结合蛋白（FKBPs）的细胞内受体家族成员形成药理活性复合物来介导的。FKBP12.FK506复合物特异性结合并抑制钙调神经磷酸酶，钙调神经磷酸酶是一种信号蛋白，在T细胞抗原受体参与时，对白介素（IL）-2基因的转录激活是必需的。FKBP12.雷帕霉素复合物与一种最近定义的靶蛋白相互作用，该靶蛋白称为雷帕霉素的哺乳动物靶标（mTOR）。越来越多的数据表明，mTOR在一条以前未被认识的信号转导途径中发挥作用，该途径是IL-2刺激的T细胞从细胞周期的G1期进入S期所必需的。在此，我们综述雷帕霉素的免疫药理学，特别强调mTOR的特性。
