Document Detail

Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway.
MedLine Citation:
PMID:  22424946     Owner:  NLM     Status:  MEDLINE    
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.
Jung Min Han; Seung Jae Jeong; Min Chul Park; Gyuyoup Kim; Nam Hoon Kwon; Hoi Kyoung Kim; Sang Hoon Ha; Sung Ho Ryu; Sunghoon Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-15
Journal Detail:
Title:  Cell     Volume:  149     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-16     Completed Date:  2012-06-08     Revised Date:  2013-09-30    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  410-24     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Medicinal Bioconvergence Research Center, Seoul National University, Seoul 151-742, Republic of Korea.
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MeSH Terms
Amino Acid Sequence
Cell Line
Cell Size
Leucine / metabolism*
Leucine-tRNA Ligase / chemistry,  metabolism*
Lysosomes / metabolism
Molecular Sequence Data
Protein Biosynthesis
Proteins / chemistry,  metabolism*
Sequence Alignment
Signal Transduction*
Reg. No./Substance:
0/Proteins; 0/mechanistic target of rapamycin complex 1; 61-90-5/Leucine; EC Ligase
Comment In:
Mol Cell. 2012 Apr 13;46(1):4-6   [PMID:  22500735 ]

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