Weisman R, Choder M
Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences. Tel Aviv University, Tel Aviv 69978, Israel.
J Biol Chem. 2001 Mar 9;276(10):7027-32. doi: 10.1074/jbc.M010446200. Epub 2000 Nov 28.
Targets of rapamycin (TORs) are conserved phosphatidylinositol kinase-related kinases that are involved in the coordination between nutritional or mitogenic signals and cell growth. Here we report the initial characterization of two Schizosaccharomyces pombe TOR homologs, tor1(+) and tor2(+). tor2(+) is an essential gene, whereas tor1(+) is required only under starvation and other stress conditions. Specifically, Deltator1 cells fail to enter stationary phase or undergo sexual development and are sensitive to cold, osmotic stress, and oxidative stress. In complex with the prolyl isomerase FKBP12, the drug rapamycin binds a conserved domain in TORs, FRB, thus inhibiting some of the functions of TORs. Mutations at a conserved serine within the FRB domain of Saccharomyces cerevisiae TOR proteins led to rapamycin resistance but did not otherwise affect the functions of the proteins. The S. pombe tor1(+) exhibits different features; substitution of the conserved serine residue, Ser(1834), with arginine compromises its functions and has no effect on the inhibition that rapamycin exerts on sexual development in S. pombe.
雷帕霉素靶蛋白（TORs）是保守的磷脂酰肌醇激酶相关激酶，参与营养或促有丝分裂信号与细胞生长之间的协调。在此，我们报道了粟酒裂殖酵母两个TOR同源物tor1(+)和tor2(+)的初步特征。tor2(+)是一个必需基因，而tor1(+)仅在饥饿和其他应激条件下才是必需的。具体而言，缺失tor1的细胞无法进入静止期或进行有性发育，并且对寒冷、渗透胁迫和氧化胁迫敏感。雷帕霉素与脯氨酰异构酶FKBP12结合后，会与TORs中的一个保守结构域FRB结合，从而抑制TORs的一些功能。酿酒酵母TOR蛋白的FRB结构域内一个保守丝氨酸发生突变会导致对雷帕霉素产生抗性，但不会影响蛋白质的其他功能。粟酒裂殖酵母tor1(+)表现出不同的特征；将保守丝氨酸残基Ser(1834)替换为精氨酸会损害其功能，并且对雷帕霉素对粟酒裂殖酵母有性发育的抑制作用没有影响。
