ArticleDevelopmental cell2020
The Rag GTPase Regulates the Dynamic Behavior of TSC Downstream of Both Amino Acid and Growth Factor Restriction.
Article in Developmental cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- mTORC1 activation induces B7-H3-dependent metabolic reprogramming in renal cell carcinoma (RCC).Oncogene · 2026Article
- GATOR2 regulates the nutrient-dependent recruitment of GATOR1 to lysosomes.bioRxiv : the preprint server for biology · 2026Article
- BoltzGen: Toward Universal Binder Design.bioRxiv : the preprint server for biology · 2025Article
- Calmodulin enhances mTORC1 signaling by preventing TSC2-Rheb binding.The Journal of biological chemistry · 2025Article
- Structure of the human TSC:WIPI3 lysosomal recruitment complex.Science advances · 2024Article
- Rag-Ragulator is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The GATOR2 complex maintains lysosomal-autophagic function by inhibiting the protein degradation of MiT/TFEs.Molecular cell · 2024Article
- The Role of mTORC1 Pathway and Autophagy in Resistance to Platinum-Based Chemotherapeutics.International journal of molecular sciences · 2023Review
- Targeting the biology of aging with mTOR inhibitors.Nature aging · 2023Review
- Regulation of mTORC1 by the Rag GTPases.Biochemical Society transactions · 2023Review
- New Insights into the Regulation of mTOR Signaling via CaInternational journal of molecular sciences · 2023Review
- Wdr59 promotes or inhibits TORC1 activity depending on cellular context.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- Renal Transcriptome and Metabolome in Mice with Principal Cell-Specific Ablation of the Tsc1 Gene: Derangements in Pathways Associated with Cell Metabolism, Growth and Acid Secretion.International journal of molecular sciences · 2022Article
- GATOR2 complex-mediated amino acid signaling regulates brain myelination.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Molecular mechanisms of dietary restriction promoting health and longevity.Nature reviews. Molecular cell biology · 2022Review
- SEA and GATOR 10 Years Later.Cells · 2021Review
- FKBP39 controls nutrient dependent Nprl3 expression and TORC1 activity in Drosophila.Cell death & disease · 2021Article
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7 authors at 2 institutions in 1 country.
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Abstract
The dysregulation of the metabolic regulator TOR complex I (TORC1) contributes to a wide array of human pathologies. Tuberous sclerosis complex (TSC) is a potent inhibitor of TORC1. Here, we demonstrate that the Rag GTPase acts in both the amino-acid-sensing and growth factor signaling pathways to control TORC1 activity through the regulation of TSC dynamics in HeLa cells and Drosophila. We find that TSC lysosomal-cytosolic exchange increases in response to both amino acid and growth factor restriction. Moreover, the rate of exchange mirrors TSC function, with depletions of the Rag GTPase blocking TSC lysosomal mobility and rescuing TORC1 activity. Finally, we show that the GATOR2 complex controls the phosphorylation of TSC2, which is essential for TSC exchange. Our data support the model that the amino acid and growth factor signaling pathways converge on the Rag GTPase to inhibit TORC1 activity through the regulation of TSC dynamics.
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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.