ArticleCell2014
Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome.
Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 515 papers.
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Who cites it
515 citing papers in PubMed, 762 citations in OpenAlex.
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- Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1.Nature communications · 2026Article
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- Ultra-Processed Diets and Pediatric Acne: Insulin-mTOR Activation and Its Potential Role in Cutaneous Inflammation.International journal of molecular sciences · 2026Review
- mTOR signaling contributes to system-driven rhythmic gene expression in mouse liver.Science advances · 2026Article
- YIF1A activates mTORC1 signaling to promote cellular senescence.Cell death & disease · 2026Article
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- Drug resistant epilepsy driven byEpilepsy & behavior reports · 2026Article
- Genetically targeted mTORC1 inhibitor reveals transcriptional control by nuclear mTORC1.Nature chemical biology · 2026Article
- ANXA11 suppression restores muscular function in the mdx mouse model of Duchenne muscular dystrophy (DMD).Nature communications · 2026Article
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Tuberous sclerosis complex.Nature reviews. Disease primers · 2026Review
- Lysosomal phosphoinositide turnover acts upstream of RagGTPase-mTORC1 and controls muscle growth.Nature metabolism · 2026Article
- Dynamic subcellular proteomics identifies regulators of adipocyte insulin action.Nature communications · 2026Article
- Peripheral lysosome levels dictate mTORC1 inactivation even when catabolically impaired.Cell communication and signaling : CCS · 2026Article
- Ratio-Driven Lipoprotein Mapping Refines Genetic Pathways of Cardiometabolic Risk.Research square · 2026Article
455 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
mTORC1 promotes cell growth in response to nutrients and growth factors. Insulin activates mTORC1 through the PI3K-Akt pathway, which inhibits the TSC1-TSC2-TBC1D7 complex (the TSC complex) to turn on Rheb, an essential activator of mTORC1. However, the mechanistic basis of how this pathway integrates with nutrient-sensing pathways is unknown. We demonstrate that insulin stimulates acute dissociation of the TSC complex from the lysosomal surface, where subpopulations of Rheb and mTORC1 reside. The TSC complex associates with the lysosome in a Rheb-dependent manner, and its dissociation in response to insulin requires Akt-mediated TSC2 phosphorylation. Loss of the PTEN tumor suppressor results in constitutive activation of mTORC1 through the Akt-dependent dissociation of the TSC complex from the lysosome. These findings provide a unifying mechanism by which independent pathways affecting the spatial recruitment of mTORC1 and the TSC complex to Rheb at the lysosomal surface serve to integrate diverse growth signals.
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Registered trials
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.