Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control
Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control
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DOI：
10.1016/s1097-2765(02)00636-6
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发表时间：
2002-09-01
期刊：
影响因子：
16
通讯作者：
Hall, MN
中科院分区：
文献类型：
--
作者：
Loewith, R;Jacinto, E;Hall, MN
酿酒酵母中雷帕霉素（TOR）蛋白的靶标TOR 1和TOR 2以雷帕霉素敏感的方式冗余地调节生长。TOR 2还以雷帕霉素不敏感的方式调节肌动蛋白细胞骨架的极化。我们描述了两个功能不同的TOR复合物。TOR复合物1（TORC 1）含有TOR 1或TOR 2、KOG 1（YHR 186 c）和LST 8。TORC 2包含TOR 2、AVO 1（YOL 078 w）、AVO 2（YMR 068 w）、AVO 3（YER 093 c）和LST 8。FKBP-雷帕霉素结合TORC 1，TORC 1破坏模拟雷帕霉素治疗，表明TORC 1介导雷帕霉素敏感的TOR共享途径。FKBP-雷帕霉素不能结合TORC 2，TORC 2破坏导致肌动蛋白缺陷，表明TORC 2介导雷帕霉素不敏感的TOR 2独特途径。因此，不同的TOR复合物解释了TOR信号传导的多样性、特异性和选择性雷帕霉素抑制。TORC 1和可能的TORC 2是从酵母到人保守的。
The target of rapamycin (TOR) proteins in Saccharomyces cerevisiae, TOR1 and TOR2, redundantly regulate growth in a rapamycin-sensitive manner. TOR2 additionally regulates polarization of the actin cytoskeleton in a rapamycin-insensitive manner. We describe two functionally distinct TOR complexes. TOR Complex 1 [TORC1) contains TOR1 or TOR2, KOG1 (YHR186c), and LST8. TORC2 contains TOR2, AVO1 (YOL078w), AVO2 (YMR068w), AVO3 (YER093c), and LST8. FKBP-rapamycin binds TORC1, and TORC1 disruption mimics rapamycin treatment, suggesting that TORC1 mediates the rapamycin-sensitive, TOR-shared pathway. FKBP-rapamycin fails to bind TORC2, and TORC2 disruption causes an actin defect, suggesting that TORC2 mediates the rapamycin-insensitive, TOR2-unique pathway. Thus, the distinct TOR complexes account for the diversity, specificity, and selective rapamycin inhibition of TOR signaling. TORC1 and possibly TORC2 are conserved from yeast to man.