ArticleeLife2016
Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 107 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
107 citing papers in PubMed, 190 citations in OpenAlex.
- Plasma metabolomic response to high-carbohydrate meals of differing glycaemic load in overweight women.European journal of nutrition · 2023Trial
- Article
- The role of L-Arginine metabolism in the hallmarks of cancer as an emerging pathway to drug design.Frontiers in pharmacology · 2026Review
- Activation of mitochondrial CPS1 promotes dormant ovarian follicle activation via arginine elevation and the mTORC1 pathway.Frontiers in cell and developmental biology · 2026Article
- Arginine shapes growth and mTOR pathway gene expression in Japanese quails (Coturnix japonica).Scientific reports · 2025Article
- Differential cell survival outcomes in response to diverse amino acid stress.Life science alliance · 2025Article
- Amino acid-dependent TSC2 dephosphorylation by lysosome-PP2A regulates mTORC1 signaling transduction.Life science alliance · 2025Article
- Endothelial Arginine Metabolism in Angiogenesis: Mechanistic Insights from Tissue Repair to Tumor Progression.Metabolites · 2025Review
- Analysis of the Stimulative Effect of Arginine on Translation Initiation of Protein Synthesis in Skeletal Muscle.Nutrients · 2025Article
- The tumor suppressor CYLD acts as a deubiquitinase for mTOR to constrain its activity.bioRxiv : the preprint server for biology · 2025Article
- Evolution of growth factor signaling to the TSC complex to regulate mTORC1.Science signaling · 2025Review
- Lysosomal EGFR acts as a Rheb-GEF independent of its kinase activity to activate mTORC1.Cell research · 2025Article
- Shared early molecular mechanisms revealed in P301S and 5xFAD Alzheimer's disease mouse models.Translational psychiatry · 2025Article
- Calmodulin enhances mTORC1 signaling by preventing TSC2-Rheb binding.The Journal of biological chemistry · 2025Article
- The endoplasmic reticulum degradation-enhancing α-mannosidase-like protein 3 attenuates the unfolded protein response and has pro-survival and pro-viral roles in hepatoma cells and hepatocellular carcinoma patients.Journal of biomedical science · 2025Article
- Arginine as host directed therapy in tuberculosis: insights from modulating arginine metabolism by supplementation and arginase inhibition.One health advances · 2025Article
- Natural Compounds and their Nano-formulations in Combating Autophagy-mediated Drug Resistance in Human Cancers.Current topics in medicinal chemistry · 2025Review
- Spatial and functional separation of mTORC1 signalling in response to different amino acid sources.Nature cell biology · 2024Article
- Site of breast cancer metastasis is independent of single nutrient levels.bioRxiv : the preprint server for biology · 2024Article
- Common epilepsy variants from the general population are not associated with epilepsy among individuals with tuberous sclerosis complex.American journal of medical genetics. Part A · 2024Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
The mammalian target of rapamycin complex 1 (mTORC1) is the key signaling hub that regulates cellular protein homeostasis, growth, and proliferation in health and disease. As a prerequisite for activation of mTORC1 by hormones and mitogens, there first has to be an available pool of intracellular amino acids. Arginine, an amino acid essential during mammalian embryogenesis and early development is one of the key activators of mTORC1. Herein, we demonstrate that arginine acts independently of its metabolism to allow maximal activation of mTORC1 by growth factors via a mechanism that does not involve regulation of mTORC1 localization to lysosomes. Instead, arginine specifically suppresses lysosomal localization of the TSC complex and interaction with its target small GTPase protein, Rheb. By interfering with TSC-Rheb complex, arginine relieves allosteric inhibition of Rheb by TSC. Arginine cooperates with growth factor signaling which further promotes dissociation of TSC2 from lysosomes and activation of mTORC1. Arginine is the main amino acid sensed by the mTORC1 pathway in several cell types including human embryonic stem cells (hESCs). Dependence on arginine is maintained once hESCs are differentiated to fibroblasts, neurons, and hepatocytes, highlighting the fundamental importance of arginine-sensing to mTORC1 signaling. Together, our data provide evidence that different growth promoting cues cooperate to a greater extent than previously recognized to achieve tight spatial and temporal regulation of mTORC1 signaling.
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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.