作者
Mee-Sup Yoon, Kook Son, Edwin Arauz, Jung Min Han, Sunghoon Kim, Jie Chen
发表日期
2016/8/9
期刊
Cell reports
卷号
16
期号
6
页码范围
1510-1517
出版商
Elsevier
简介
Amino acid availability activates signaling by the mammalian target of rapamycin (mTOR) complex 1, mTORC1, a master regulator of cell growth. The class III PI-3-kinase Vps34 mediates amino acid signaling to mTORC1 by regulating lysosomal translocation and activation of the phospholipase PLD1. Here, we identify leucyl-tRNA synthetase (LRS) as a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS is necessary for amino acid-induced Vps34 activation, cellular PI(3)P level increase, PLD1 activation, and PLD1 lysosomal translocation. Leucine binding, but not tRNA charging activity of LRS, is required for this regulation. Moreover, LRS physically interacts with Vps34 in amino acid-stimulatable non-autophagic complexes. Finally, purified LRS protein activates Vps34 kinase in vitro in a leucine-dependent manner. Collectively, our findings provide compelling evidence for a direct role of …
学术搜索中的文章
MS Yoon, K Son, E Arauz, JM Han, S Kim, J Chen - Cell reports, 2016