PMID- 20381137
OWN - NLM
STAT- MEDLINE
DCOM- 20100504
LR  - 20231213
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 141
IP  - 2
DP  - 2010 Apr 16
TI  - Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary 
      for its activation by amino acids.
PG  - 290-303
LID - 10.1016/j.cell.2010.02.024 [doi]
AB  - The mTORC1 kinase promotes growth in response to growth factors, energy levels, 
      and amino acids, and its activity is often deregulated in disease. The Rag 
      GTPases interact with mTORC1 and are proposed to activate it in response to amino 
      acids by promoting mTORC1 translocation to a membrane-bound compartment that 
      contains the mTORC1 activator, Rheb. We show that amino acids induce the movement 
      of mTORC1 to lysosomal membranes, where the Rag proteins reside. A complex 
      encoded by the MAPKSP1, ROBLD3, and c11orf59 genes, which we term Ragulator, 
      interacts with the Rag GTPases, recruits them to lysosomes, and is essential for 
      mTORC1 activation. Constitutive targeting of mTORC1 to the lysosomal surface is 
      sufficient to render the mTORC1 pathway amino acid insensitive and independent of 
      Rag and Ragulator, but not Rheb, function. Thus, Rag-Ragulator-mediated 
      translocation of mTORC1 to lysosomal membranes is the key event in amino acid 
      signaling to mTORC1.
CI  - Copyright 2010 Elsevier Inc. All rights reserved.
FAU - Sancak, Yasemin
AU  - Sancak Y
AD  - Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 
      02142, USA.
FAU - Bar-Peled, Liron
AU  - Bar-Peled L
FAU - Zoncu, Roberto
AU  - Zoncu R
FAU - Markhard, Andrew L
AU  - Markhard AL
FAU - Nada, Shigeyuki
AU  - Nada S
FAU - Sabatini, David M
AU  - Sabatini DM
LA  - eng
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - CA103866/CA/NCI NIH HHS/United States
GR  - DP2 ES032761/ES/NIEHS NIH HHS/United States
GR  - R37 AI047389/AI/NIAID NIH HHS/United States
GR  - R01 CA129105/CA/NCI NIH HHS/United States
GR  - AI47389/AI/NIAID NIH HHS/United States
GR  - R01 CA103866-01/CA/NCI NIH HHS/United States
GR  - R01 AI047389-01/AI/NIAID NIH HHS/United States
GR  - R01 AI047389/AI/NIAID NIH HHS/United States
GR  - R01 CA103866/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20100408
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Amino Acids)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (LAMP2 protein, human)
RN  - 0 (LAMTOR3 protein, human)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Lysosomal Membrane Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Neuropeptides)
RN  - 0 (Proteins)
RN  - 0 (RHEB protein, human)
RN  - 0 (RPTOR protein, human)
RN  - 0 (Ras Homolog Enriched in Brain Protein)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
SB  - IM
CIN - Cell Metab. 2010 May 5;11(5):341-2. PMID: 20444413
CIN - Nat Rev Mol Cell Biol. 2010 Jun;11(6):388. PMID: 20445544
CIN - Nat Rev Cancer. 2010 Jun;10(6):381. PMID: 20506585
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Amino Acids/metabolism
MH  - Animals
MH  - Cell Line
MH  - Drosophila
MH  - Humans
MH  - Intracellular Membranes/metabolism
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Lysosomal-Associated Membrane Protein 2
MH  - Lysosomal Membrane Proteins/metabolism
MH  - Lysosomes/*metabolism
MH  - MAP Kinase Signaling System
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Models, Biological
MH  - Monomeric GTP-Binding Proteins/metabolism
MH  - Multiprotein Complexes
MH  - Mutation
MH  - Neuropeptides/metabolism
MH  - Protein Binding
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Protein Transport
MH  - Proteins/genetics/metabolism
MH  - Ras Homolog Enriched in Brain Protein
MH  - Recombinant Proteins/genetics/metabolism
MH  - Regulatory-Associated Protein of mTOR
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors/genetics/*metabolism
PMC - PMC3024592
MID - NIHMS200582
EDAT- 2010/04/13 06:00
MHDA- 2010/05/05 06:00
PMCR- 2011/01/21
CRDT- 2010/04/13 06:00
PHST- 2009/10/16 00:00 [received]
PHST- 2009/12/28 00:00 [revised]
PHST- 2010/02/05 00:00 [accepted]
PHST- 2010/04/13 06:00 [entrez]
PHST- 2010/04/13 06:00 [pubmed]
PHST- 2010/05/05 06:00 [medline]
PHST- 2011/01/21 00:00 [pmc-release]
AID - S0092-8674(10)00177-7 [pii]
AID - 10.1016/j.cell.2010.02.024 [doi]
PST - ppublish
SO  - Cell. 2010 Apr 16;141(2):290-303. doi: 10.1016/j.cell.2010.02.024. Epub 2010 Apr 
      8.