Document Detail


Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1.
MedLine Citation:
PMID:  22980980     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to numerous cues, including amino acids, which promote mTORC1 translocation to the lysosomal surface, its site of activation. The heterodimeric RagA/B-RagC/D GTPases, the Ragulator complex that tethers the Rags to the lysosome, and the v-ATPase form a signaling system that is necessary for amino acid sensing by mTORC1. Amino acids stimulate the binding of guanosine triphosphate to RagA and RagB but the factors that regulate Rag nucleotide loading are unknown. Here, we identify HBXIP and C7orf59 as two additional Ragulator components that are required for mTORC1 activation by amino acids. The expanded Ragulator has nucleotide exchange activity toward RagA and RagB and interacts with the Rag heterodimers in an amino acid- and v-ATPase-dependent fashion. Thus, we provide mechanistic insight into how mTORC1 senses amino acids by identifying Ragulator as a guanine nucleotide exchange factor (GEF) for the Rag GTPases.
Authors:
Liron Bar-Peled; Lawrence D Schweitzer; Roberto Zoncu; David M Sabatini
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Cell     Volume:  150     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-17     Completed Date:  2012-11-23     Revised Date:  2014-03-28    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1196-208     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / chemistry,  metabolism*
Amino Acid Sequence
Amino Acids / metabolism*
Animals
Drosophila / metabolism*
GTP Phosphohydrolases / metabolism
Guanine Nucleotide Exchange Factors / chemistry,  metabolism*
HEK293 Cells
Humans
Molecular Sequence Data
Multiprotein Complexes
Proteins / metabolism*
Signal Transduction*
TOR Serine-Threonine Kinases
Grant Support
ID/Acronym/Agency:
AI47389/AI/NIAID NIH HHS; CA103866/CA/NCI NIH HHS; F31 CA167872/CA/NCI NIH HHS; F31CA167872/CA/NCI NIH HHS; R01 AI047389/AI/NIAID NIH HHS; R01 CA103866/CA/NCI NIH HHS; R01 CA129105/CA/NCI NIH HHS; R37 AI047389/AI/NIAID NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Amino Acids; 0/C7orf59 protein, human; 0/Guanine Nucleotide Exchange Factors; 0/HBXIP protein, human; 0/Multiprotein Complexes; 0/Proteins; 0/mechanistic target of rapamycin complex 1; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 3.6.1.-/GTP Phosphohydrolases
Comments/Corrections

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