基-tRNA合成酶是mTORC1信号通路的细胞内素传感器
Jung Min Han1, Seung Jae Jeong, Min Chul Park
1Medicinal Bioconvergence Research Center, Seoul National University, Seoul 151-742, Republic of Korea.
Cell
|March 20, 2012
概括
基-tRNA合成酶 (LRS) 作为mTORC1通路的氨基酸传感器. LRS直接激活Rag GTPase,通过氨基酸诱导的mTORC1信号传递进行中介.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 氨基酸对于激活哺乳动物中拉巴胺素 (mTOR) 激酶的标是必不可少的.
- mTOR调节关键的细胞过程,包括蛋白质翻译,细胞大小和自.
- 特定的细胞内氨基酸传感器直接将氨基酸水平与mTORC1联系在一起仍然未确定.
研究的目的:
- 为了识别直接的传感器,将细胞内氨基酸度与mTORC1通路连接起来.
- 阐明氨基酸感应激活mTORC1.1.的机制.
主要方法:
- 研究了白-tRNA合成酶 (LRS) 在氨基酸诱导的mTORC1激活中的作用.
- 利用位点定向突变发生法来评估LRS白结合残留的重要性.
- 使用生物化学测试检查了LRS和Rag GTPase之间的相互作用.
- 确定了LRS对Rag GTPase的GTPase激活蛋白 (GAP) 活性.
主要成果:
- 基-tRNA合成酶 (LRS) 作为细胞内氨酸度的关键传感器.
- 在LRS的白结合部位的突变取消了氨基酸依赖的mTORC1激活.
- LRS以氨基酸依赖的方式直接与Rag GTPase结合.
- LRS对Rag GTPase表现出GTPase激活蛋白 (GAP) 的活性,从而促进mTORC1的激活.
结论:
- 基-tRNA合成酶 (LRS) 被确定为mTORC1通路的氨基酸介导激活的关键传感器.
- 通过激活Rag GTPase,LRS直接将细胞内氨基酸水平与mTORC1信号联系起来.
- 这一发现提供了营养可用性和细胞生长调节之间的关键机制联系.
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