| Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. | |
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MedLine Citation:
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PMID: 22980980 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Liron Bar-Peled; Lawrence D Schweitzer; Roberto Zoncu; David M Sabatini |
Publication Detail:
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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:
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Title: Cell Volume: 150 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-09-17 Completed Date: 2012-11-23 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 1196-208 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center, Cambridge, MA 02142, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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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 Proteins / metabolism* Signal Transduction* |
| Grant Support | |
ID/Acronym/Agency:
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AI47389/AI/NIAID NIH HHS; CA103866/CA/NCI NIH HHS; F31CA167872/CA/NCI NIH HHS; R01 AI047389/AI/NIAID NIH HHS; R01 CA103866/CA/NCI NIH HHS; R37 AI047389/AI/NIAID NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/Amino Acids; 0/C7orf59 protein, human; 0/Guanine Nucleotide Exchange Factors; 0/HBXIP protein, human; 0/Proteins; 0/mTORC1 complex, human; EC 3.6.1.-/GTP Phosphohydrolases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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