Aspuria Paul-Joseph, Sato Tatsuhiro, Tamanoi Fuyuhiko
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, California 90095-1489, USA.
Cell Cycle. 2007 Jul 15;6(14):1692-5. doi: 10.4161/cc.6.14.4478. Epub 2007 May 21.
The TSC/Rheb/TOR signaling pathway plays important roles in growth and cell cycle regulation. The main player TOR belongs to the PI3K-related protein kinase family. Recent studies utilizing fission yeast Tor2 have led to the identification of a number of amino acid changes that lead to inactivation as well as activation of TOR kinase. Also, constitutive active mutations in its upstream regulator, Rheb, have been identified. Isolation and characterization of temperature sensitive Tor2 mutants have established that this kinase functions as a key switch that determines cell fate between growth and sexual development. Introduction of Tor2 activating mutations into mTOR conferred nutrient independent activation of mTOR. Interestingly, these studies point to regions of TOR kinase important for its function.
TSC/Rheb/TOR信号通路在生长和细胞周期调控中发挥着重要作用。主要参与者TOR属于PI3K相关蛋白激酶家族。最近利用裂殖酵母Tor2进行的研究已鉴定出一些导致TOR激酶失活以及激活的氨基酸变化。此外，还鉴定出了其上游调节因子Rheb中的组成型活性突变。温度敏感型Tor2突变体的分离和表征已证实该激酶作为一个关键开关，决定细胞在生长和有性发育之间的命运。将Tor2激活突变引入mTOR可使mTOR获得营养物非依赖性激活。有趣的是，这些研究指出了TOR激酶对其功能重要的区域。
