PMID- 22424946
OWN - NLM
STAT- MEDLINE
DCOM- 20120608
LR  - 20220408
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Linking)
VI  - 149
IP  - 2
DP  - 2012 Apr 13
TI  - Leucyl-tRNA synthetase is an intracellular leucine sensor for the 
      mTORC1-signaling pathway.
PG  - 410-24
LID - 10.1016/j.cell.2012.02.044 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Han, Jung Min
AU  - Han JM
AD  - Medicinal Bioconvergence Research Center, Seoul National University, Seoul 
      151-742, Republic of Korea.
FAU - Jeong, Seung Jae
AU  - Jeong SJ
FAU - Park, Min Chul
AU  - Park MC
FAU - Kim, Gyuyoup
AU  - Kim G
FAU - Kwon, Nam Hoon
AU  - Kwon NH
FAU - Kim, Hoi Kyoung
AU  - Kim HK
FAU - Ha, Sang Hoon
AU  - Ha SH
FAU - Ryu, Sung Ho
AU  - Ryu SH
FAU - Kim, Sunghoon
AU  - Kim S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120315
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Proteins)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 6.1.1.4 (Leucine-tRNA Ligase)
RN  - GMW67QNF9C (Leucine)
SB  - IM
CIN - Mol Cell. 2012 Apr 13;46(1):4-6. PMID: 22500735
MH  - Amino Acid Sequence
MH  - Animals
MH  - Autophagy
MH  - Cell Line
MH  - Cell Size
MH  - Humans
MH  - Leucine/*metabolism
MH  - Leucine-tRNA Ligase/chemistry/*metabolism
MH  - Lysosomes/metabolism
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Molecular Sequence Data
MH  - Multiprotein Complexes
MH  - Protein Biosynthesis
MH  - Proteins/chemistry/*metabolism
MH  - Sequence Alignment
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases
EDAT- 2012/03/20 06:00
MHDA- 2012/06/09 06:00
CRDT- 2012/03/20 06:00
PHST- 2011/04/29 00:00 [received]
PHST- 2011/07/31 00:00 [revised]
PHST- 2012/02/22 00:00 [accepted]
PHST- 2012/03/20 06:00 [entrez]
PHST- 2012/03/20 06:00 [pubmed]
PHST- 2012/06/09 06:00 [medline]
AID - S0092-8674(12)00282-6 [pii]
AID - 10.1016/j.cell.2012.02.044 [doi]
PST - ppublish
SO  - Cell. 2012 Apr 13;149(2):410-24. doi: 10.1016/j.cell.2012.02.044. Epub 2012 Mar 
      15.