拉格GTPases与猛禽结合,并将氨基酸信号传递到mTORC1中
Yasemin Sancak1, Timothy R Peterson, Yoav D Shaul
1Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology (MIT), Nine Cambridge Center, Cambridge, MA 02142, USA.
Science (New York, N.Y.)
|May 24, 2008
概括
拉格蛋白对于激活mTORC1通路来响应氨基酸是必不可少的. 这些GTPase调解mTORC1局部化,影响细胞生长和癌症途径.
科学领域:
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
- 生物化学 生物化学
背景情况:
- 拉巴胺素复合体1 (mTORC1) 途径的机械性标调节细胞生长.
- 这条通路对氨基酸,胰岛素和能量水平等营养物质做出反应.
- mTORC1失调与各种癌症有关.
研究的目的:
- 研究Rag蛋白在mTORC1通路激活中的作用.
- 为了确定氨基酸如何通过Rag蛋白向mTORC1.1发出信号.
- 为了阐明拉格介导的mTORC1调节的机制.
主要方法:
- 利用突变的Rag蛋白 (GTP结合和GDP结合) 来研究mTORC1的活动.
- 评估了mTORC1通路激活和细胞内定位.
- 研究了Rag蛋白和mTORC1.1.之间的相互作用.
主要成果:
- 拉格蛋白与mTORC1以氨基酸依赖的方式相互作用.
- 构成性活跃的与GTP结合的Rag蛋白可以独立于氨基酸激活mTORC1.
- 与GDP结合的Rag蛋白抑制了氨基酸刺激的mTORC1激活.
- 拉格蛋白促进mTORC1局部化到与Rheb,其激活器.
结论:
- 拉格蛋白是氨基酸向mTORC1.1.的信号传递的关键媒介.
- 拉格蛋白通过促进mTORC1.1.的适当细胞内定位而起作用.
- 了解Rag-mTORC1相互作用是针对癌症生长途径的关键.
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