Amino acids are required for activation of the mammalian target of rapamycin 
(mTOR) kinase, which regulates protein translation, cell size, and autophagy. 
However, the amino acid sensor that directly couples intracellular amino 
acid-mediated signaling to mTORC1 is unknown. Here we show that leucyl-tRNA 
synthetase (LRS) plays a critical role in amino acid-induced mTORC1 activation 
by sensing intracellular leucine concentration and initiating molecular events 
leading to mTORC1 activation. Mutation of LRS amino acid residues important for 
leucine binding renders the mTORC1 pathway insensitive to intracellular levels 
of amino acids. We show that LRS directly binds to Rag GTPase, the mediator of 
amino acid signaling to mTORC1, in an amino acid-dependent manner and functions 
as a GTPase-activating protein (GAP) for Rag GTPase to activate mTORC1. This 
work demonstrates that LRS is a key mediator for amino acid signaling to mTORC1.