Flanagan W M, Crabtree G R
Howard Hughes Medical Institute, Beckman Center, Stanford University Medical School, California 94025.
Ann N Y Acad Sci. 1993 Nov 30;696:31-7. doi: 10.1111/j.1749-6632.1993.tb17139.x.
Rapamycin, a potent immunosuppressant and antifungal agent, inhibits an evolutionarily conserved mechanism regulating cell cycle progression. In an interleukin-2 (IL-2) dependent murine T cell, we demonstrate that rapamycin arrested T cells prior to the entry into S-phase of the cell cycle and that rapamycin inhibited the IL-2-stimulated expression of p34cdc2, a serine/threonine kinase that is required for cells to progress through the cell cycle. The mechanism of action of rapamycin appeared specific since the structural analogue and immunosuppressant FK506 had no effect on the progression of the cells through S-phase or the expression of p34cdc2. These results demonstrate a rapamycin-sensitive IL-2-dependent signaling pathway in T cells and suggest that the immunosuppressive properties of rapamycin are mediated by impinging on the IL-2-induced T cell expression of p34cdc2.
雷帕霉素是一种强效免疫抑制剂和抗真菌剂，它能抑制一种在进化上保守的调节细胞周期进程的机制。在依赖白细胞介素-2（IL-2）的小鼠T细胞中，我们证明雷帕霉素在T细胞进入细胞周期的S期之前使其停滞，并且雷帕霉素抑制了IL-2刺激的p34cdc2的表达，p34cdc2是一种丝氨酸/苏氨酸激酶，细胞在细胞周期进程中需要它。雷帕霉素的作用机制似乎具有特异性，因为其结构类似物和免疫抑制剂FK506对细胞通过S期的进程或p34cdc2的表达没有影响。这些结果证明了T细胞中存在一条对雷帕霉素敏感的IL-2依赖性信号通路，并表明雷帕霉素的免疫抑制特性是通过影响IL-2诱导的T细胞中p34cdc2的表达来介导的。
