猛龙,一个绑定合作伙伴的目标的拉帕米辛 (TOR),调解TOR的行动
Kenta Hara1, Yoshiko Maruki, Xiaomeng Long
1Biosignal Research Center, Kobe University, 657-8501, Kobe, Japan. harak@kobe-u.ac.jp
Cell
|August 2, 2002
概括
猛禽是一种关键的蛋白质支架,它与mTOR结合,使其能够酸化关键标,如4EBP1. 这种相互作用对于调节细胞生长和调节TOR信号在体内至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 生物化学 生物化学
背景情况:
- 拉巴胺素 (mTOR) 途径的机械性标是细胞生长,增殖和新陈代谢的中央调节者.
- mTOR的主要下游目标包括p70 S6激酶α (p70alpha) 和真核细胞启动因子4E结合蛋白1 (4EBP1).
- 了解mTOR活动的调节机制对于理解细胞平衡和疾病状态至关重要.
研究的目的:
- 为了研究Raptor的作用,一个mTOR结合蛋白,在调节mTOR激酶活性.
- 为了阐明猛龙调解mTOR信号的机制.
- 为了确定猛龙在细胞过程中的体内功能.
主要方法:
- 试管体内激酶试验评估mTOR对p70alpha和4EBP1.1的活性.
- 同免疫沉和拉下测试用于研究蛋白质-蛋白质相互作用.
- 细胞培养中的RNA干扰 (RNAi) 抑制猛禽表达.
- 在Caenorhabditis elegans (C. elegans) 中的RNAi用于研究体内表型.
主要成果:
- 猛龙直接与mTOR结合,并且在体外对4EBP1进行有效的mTOR催化酸化是必要的.
- 猛禽结合增强了对p70alpha.alpha的mTOR激酶活性.
- 通过RNAi对Raptor表达的部分抑制减少了mTOR催化的4EBP1酸化.
- 在C. elegans中,RNAi介导的Raptor无活化重复了Ce-TOR无活化时观察到的表型.
结论:
- 猛禽的功能是mTOR的重要支架蛋白,促进其基质的酸化,特别是4EBP1.1.
- 猛禽是mTOR (TOR) 在体内信号传递的关键媒介.
- 这些发现强调了Raptor在控制细胞生长和TOR通路输出的不可或缺的作用.
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