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Differential regulation of mTORC1 by leucine and glutamine

2015· article· en· 744 citations· W2157760261 on OpenAlex· 10.1126/science.1259472

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Abstract

The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates environmental and intracellular signals to regulate cell growth. Amino acids stimulate mTORC1 activation at the lysosome in a manner thought to be dependent on the Rag small guanosine triphosphatases (GTPases), the Ragulator complex, and the vacuolar H(+)-adenosine triphosphatase (v-ATPase). We report that leucine and glutamine stimulate mTORC1 by Rag GTPase-dependent and -independent mechanisms, respectively. Glutamine promoted mTORC1 translocation to the lysosome in RagA and RagB knockout cells and required the v-ATPase but not the Ragulator. Furthermore, we identified the adenosine diphosphate ribosylation factor-1 GTPase to be required for mTORC1 activation and lysosomal localization by glutamine. Our results uncover a signaling cascade to mTORC1 activation independent of the Rag GTPases and suggest that mTORC1 is differentially regulated by specific amino acids.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Science
Topic
PI3K/AKT/mTOR signaling in cancer
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
Funders
National Institute of General Medical SciencesNational Institutes of HealthNational Cancer InstituteCanadian Institutes of Health ResearchHartwell FoundationNational Institute of Diabetes and Digestive and Kidney DiseasesU.S. Department of Defense
Keywords
mTORC1GTPaseGlutamineLeucineAmino acidGuanosineBiochemistryTriphosphataseCell biologyBiologyChemistrySignal transductionPI3K/AKT/mTOR pathway
Has abstract in OpenAlex
yes