ArticleNature communications2018
Src regulates amino acid-mediated mTORC1 activation by disrupting GATOR1-Rag GTPase interaction.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Sex-stratified genome-wide meta-analysis identifies novel loci for cognitive decline in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- METTL1-mediated mOncogene · 2026Article
- Fibrosis and Src Signalling in Glaucoma: From Molecular Pathways to Therapeutic Prospects.International journal of molecular sciences · 2025Review
- Identifying the Pathogenicity of a Novel NPRL3 Missense Mutation Using Personalized Cortical Organoid Model of Focal Cortical Dysplasia.Journal of molecular neuroscience : MN · 2024Article
- Phylogenetic Relations and High-Altitude Adaptation in Wild Boar (Animals : an open access journal from MDPI · 2024Article
- Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.Autophagy · 2024Article
- NRF2 connects Src tyrosine kinase to ferroptosis resistance in glioblastoma.Life science alliance · 2024Article
- Phosphorylation of OTUB1 at Tyr 26 stabilizes the mTORC1 component, Raptor.Cell death and differentiation · 2023Article
- NPRL2 down-regulation facilitates the growth of hepatocellular carcinoma via the mTOR pathway and autophagy suppression.Hepatology communications · 2022Article
- Src: coordinating metabolism in cancer.Oncogene · 2022Review
- Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-Life (Basel, Switzerland) · 2022Article
- Pan-Src kinase inhibitor treatment attenuates diabetic kidney injury via inhibition of Fyn kinase-mediated endoplasmic reticulum stress.Experimental & molecular medicine · 2022Article
- Src Family Kinases: A Potential Therapeutic Target for Acute Kidney Injury.Biomolecules · 2022Review
- Cell adhesion suppresses autophagy via Src/FAK-mediated phosphorylation and inhibition of AMPK.Cellular signalling · 2022Article
- Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment.BMC molecular and cell biology · 2021Article
- The mTOR Pathway in Pluripotent Stem Cells: Lessons for Understanding Cancer Cell Dormancy.Membranes · 2021Review
- SEA and GATOR 10 Years Later.Cells · 2021Review
- Article
- Amino Acids in Autophagy: Regulation and Function.Advances in experimental medicine and biology · 2021Article
- Advances in the Role of Leucine-Sensing in the Regulation of Protein Synthesis in Aging Skeletal Muscle.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell survival and autophagy, and its activity is regulated by amino acid availability. Rag GTPase-GATOR1 interactions inhibit mTORC1 in the absence of amino acids, and GATOR1 release and activation of RagA/B promotes mTORC1 activity in the presence of amino acids. However, the factors that play a role in Rag-GATOR1 interaction are still poorly characterized. Here, we show that the tyrosine kinase Src is crucial for amino acid-mediated activation of mTORC1. Src acts upstream of the Rag GTPases by promoting dissociation of GATOR1 from the Rags, thereby determining mTORC1 recruitment and activation at the lysosomal surface. Accordingly, amino acid-mediated regulation of Src/mTORC1 modulates autophagy and cell size expansion. Finally, Src hyperactivation overrides amino acid signaling in the activation of mTORC1. These results shed light on the mechanisms underlying pathway dysregulation in many cancer types.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.