Nguyen Thu P, Frank Anderson R, Jewell Jenna L
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX USA.
Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX USA.
Cell Logist. 2017 Sep 29;7(4):e1378794. doi: 10.1080/21592799.2017.1378794. eCollection 2017.
The mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that belongs to the phosphatidylinositol 3-kinase-related kinase (PIKK) family. mTOR is the catalytic subunit of mTOR complex 1 (mTORC1), which integrates multiple environmental signals to control cell growth and metabolism. Nutrients, specifically amino acids, are the most potent stimuli for mTORC1 activation. Multiple studies have focused on how leucine and arginine activate mTORC1 through the Rag GTPases, with mechanistic details slowly emerging. Recently, a Rag GTPase-independent glutamine signaling pathway to mTORC1 has been identified, suggesting that mTORC1 is differentially regulated through distinct pathways by specific amino acids. In this review, we summarize our current understanding of how amino acids modulate mTORC1, and the role of other small GTPases in the regulation of mTORC1 activity.
雷帕霉素哺乳动物靶蛋白（mTOR）是一种在进化上保守的丝氨酸/苏氨酸激酶，属于磷脂酰肌醇3激酶相关激酶（PIKK）家族。mTOR是mTOR复合物1（mTORC1）的催化亚基，该复合物整合多种环境信号以控制细胞生长和代谢。营养物质，特别是氨基酸，是mTORC1激活的最有效刺激因素。多项研究聚焦于亮氨酸和精氨酸如何通过Rag GTP酶激活mTORC1，其机制细节正逐渐明晰。最近，一条不依赖Rag GTP酶的谷氨酰胺信号通路被发现可作用于mTORC1，这表明mTORC1受特定氨基酸通过不同途径的差异调节。在本综述中，我们总结了目前对氨基酸如何调节mTORC1的理解，以及其他小GTP酶在mTORC1活性调节中的作用。
