Helliwell S B, Wagner P, Kunz J, Deuter-Reinhard M, Henriquez R, Hall M N
Department of Biochemistry, University of Basel, Switzerland.
Mol Biol Cell. 1994 Jan;5(1):105-18. doi: 10.1091/mbc.5.1.105.
The Saccharomyces cerevisiae genes TOR1 and TOR2 were originally identified by mutations that confer resistance to the immunosuppressant rapamycin. TOR2 was previously shown to encode an essential 282-kDa phosphatidylinositol kinase (PI kinase) homologue. The TOR1 gene product is also a large (281 kDa) PI kinase homologue, with 67% identity to TOR2. TOR1 is not essential, but a TOR1 TOR2 double disruption uniquely confers a cell cycle (G1) arrest as does exposure to rapamycin; disruption of TOR2 alone is lethal but does not cause a cell cycle arrest. TOR1-TOR2 and TOR2-TOR1 hybrids indicate that carboxy-terminal domains of TOR1 and TOR2 containing a lipid kinase sequence motif are interchangeable and therefore functionally equivalent; the other portions of TOR1 and TOR2 are not interchangeable. The TOR1-1 and TOR2-1 mutations, which confer rapamycin resistance, alter the same potential protein kinase C site in the respective protein's lipid kinase domain. Thus, TOR1 and TOR2 are likely similar but not identical, rapamycin-sensitive PI kinases possibly regulated by phosphorylation. TOR1 and TOR2 may be components of a novel signal transduction pathway controlling progression through G1.
酿酒酵母基因TOR1和TOR2最初是通过赋予对免疫抑制剂雷帕霉素抗性的突变而被鉴定出来的。先前已表明TOR2编码一种必需的282 kDa磷脂酰肌醇激酶（PI激酶）同源物。TOR1基因产物也是一种大型（281 kDa）PI激酶同源物，与TOR2有67%的同一性。TOR1不是必需的，但TOR1 TOR2双缺失与暴露于雷帕霉素一样，独特地导致细胞周期（G1）停滞；单独破坏TOR2是致死的，但不会导致细胞周期停滞。TOR1 - TOR2和TOR2 - TOR1杂种表明，TOR1和TOR2含有脂质激酶序列基序的羧基末端结构域是可互换的，因此在功能上是等效的；TOR1和TOR2的其他部分不可互换。赋予雷帕霉素抗性的TOR1 - 1和TOR2 - 1突变改变了各自蛋白质脂质激酶结构域中相同的潜在蛋白激酶C位点。因此，TOR1和TOR2可能相似但不相同，可能是受磷酸化调节的雷帕霉素敏感PI激酶。TOR1和TOR2可能是控制G1期进程的新型信号转导途径的组成部分。
