Zheng X F, Florentino D, Chen J, Crabtree G R, Schreiber S L
Howard Hughes Medical Institute Department of Chemistry, Harvard University Cambridge, Massachusetts 02138, USA.
Cell. 1995 Jul 14;82(1):121-30. doi: 10.1016/0092-8674(95)90058-6.
The rapamycin-sensitive signaling pathway is required to transduce specific mitogenic signals to the cell cycle machinery responsible for G1 progression. Genetic studies in yeast identified two related genes on this pathway, TOR1 and TOR2, thought to encode novel phosphatidylinositol kinases. We now show that an intact kinase domain is required for the G1 cell cycle functions of both proteins, for the ability of a mutation in a neighboring FKBP12-rapamycin-binding domain of the TOR1 protein to inhibit the growth of yeast cells when overexpressed, and for the essential function of the TOR2 protein. The G1 function of both TOR proteins is sensitive to rapamycin, but the essential function of TOR2 is not. Thus, FKBP12-rapamycin does not appear to inhibit the kinase activity of TOR proteins in a general way; instead, it may interfere selectively with TOR protein binding to or phosphorylation of G1 effectors.
雷帕霉素敏感信号通路需要将特定的促有丝分裂信号转导至负责G1期进程的细胞周期机制。酵母中的遗传学研究在该通路上鉴定出两个相关基因，TOR1和TOR2，它们被认为编码新型磷脂酰肌醇激酶。我们现在表明，完整的激酶结构域对于这两种蛋白质的G1期细胞周期功能、对于TOR1蛋白相邻的FKBP12-雷帕霉素结合结构域中的突变在过表达时抑制酵母细胞生长的能力以及对于TOR2蛋白的基本功能都是必需的。两种TOR蛋白的G1期功能对雷帕霉素敏感，但TOR2的基本功能则不然。因此，FKBP12-雷帕霉素似乎并非以普遍方式抑制TOR蛋白的激酶活性；相反，它可能选择性地干扰TOR蛋白与G1期效应物的结合或磷酸化。
