Helliwell S B, Howald I, Barbet N, Hall M N
Department of Biochemistry, Biozentrum, University of Basel, Switzerland.
Genetics. 1998 Jan;148(1):99-112. doi: 10.1093/genetics/148.1.99.
The Saccharomyces cerevisiae genes TOR1 and TOR2 encode phosphatidylinositol kinase homologs. TOR2 has two essential functions. One function overlaps with TOR1 and mediates protein synthesis and cell cycle progression. The second essential function of TOR2 is unique to TOR2 and mediates the cell-cycle-dependent organization of the actin cytoskeleton. We have isolated temperature-sensitive mutants that are defective for either one or both of the two TOR2 functions. The three classes of mutants were as follows. Class A mutants, lacking only the TOR2-unique function, are defective in actin cytoskeleton organization and arrest within two to three generations as small-budded cells in the G2/M phase of the cell cycle. Class B mutants, lacking only the TOR-shared function, and class C mutants, lacking both functions, exhibit a rapid loss of protein synthesis and a G1 arrest within one generation. To define further the two functions of TOR2, we isolated multicopy suppressors that rescue the class A or B mutants. Overexpression of MSS4, PKC1, PLC1, RHO2, ROM2, or SUR1 suppressed the growth defect of a class A mutant. Surprisingly, overexpression of PLC1 and MSS4 also suppressed the growth defect of a class B mutant. These genes encode proteins that are involved in phosphoinositide metabolism and signaling. Thus, the two functions (readouts) of TOR2 appear to involve two related signaling pathways controlling cell growth.
酿酒酵母基因TOR1和TOR2编码磷脂酰肌醇激酶同源物。TOR2有两个基本功能。一个功能与TOR1重叠，介导蛋白质合成和细胞周期进程。TOR2的第二个基本功能是TOR2特有的，介导肌动蛋白细胞骨架的细胞周期依赖性组织。我们分离出了对TOR2的两种功能中的一种或两种有缺陷的温度敏感突变体。这三类突变体如下。A类突变体仅缺乏TOR2特有的功能，在肌动蛋白细胞骨架组织方面有缺陷，并在两到三代内停滞为细胞周期G2/M期的小芽细胞。B类突变体仅缺乏TOR共享的功能，C类突变体两种功能均缺乏，在一代内表现出蛋白质合成迅速丧失和G1期停滞。为了进一步定义TOR2的两种功能，我们分离出了能挽救A类或B类突变体的多拷贝抑制子。MSS4、PKC1、PLC1、RHO2、ROM2或SUR1的过表达抑制了A类突变体的生长缺陷。令人惊讶的是，PLC1和MSS4的过表达也抑制了B类突变体的生长缺陷。这些基因编码参与磷酸肌醇代谢和信号传导的蛋白质。因此，TOR2的两种功能（读数）似乎涉及控制细胞生长的两条相关信号通路。
