ArticleThe Journal of biological chemistry2009
Specific activation of mTORC1 by Rheb G-protein in vitro involves enhanced recruitment of its substrate protein.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 194 citations in OpenAlex.
- A standardized randomized 6-month aerobic exercise-training down-regulated pro-inflammatory genes, but up-regulated anti-inflammatory, neuron survival and axon growth-related genes.Experimental gerontology · 2015Trial
- LAT1/SLC7A5-mediated amino acid uptake is regulated by redox signals triggered by formyl-peptide receptor 2.The FEBS journal · 2026Article
- Tuberous sclerosis complex.Nature reviews. Disease primers · 2026Review
- Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets.Cells · 2024Review
- Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.International journal of molecular sciences · 2024Review
- IGF/mTORC1/S6 Signaling Is Potentiated and Prolonged by Acute Loading of Subtoxicological Manganese Ion.Biomolecules · 2023Article
- Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System.Biomolecules · 2023Review
- Constitutive activation of TORC1 signalling attenuates virulence in the cross-kingdom fungal pathogen Fusarium oxysporum.Molecular plant pathology · 2023Article
- Causal relationship between insulin resistance and sarcopenia.Diabetology & metabolic syndrome · 2023Review
- The Metabolic Basis for Nervous System Dysfunction in Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.Current neurovascular research · 2023Article
- Insulin-induced mTOR signaling and gluconeogenesis in renal proximal tubules: A mini-review of current evidence and therapeutic potential.Frontiers in pharmacology · 2022Review
- Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma.Frontiers in molecular neuroscience · 2022Review
- Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021Review
- The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions.Cancers · 2021Review
- Pib2 as an Emerging Master Regulator of Yeast TORC1.Biomolecules · 2021Review
- Article
- Evaluation of the Binding Kinetics of RHEB with mTORC1 by In-Cell and In Vitro Assays.International journal of molecular sciences · 2021Article
- Glucagon transiently stimulates mTORC1 by activation of an EPAC/Rap1 signaling axis.Cellular signalling · 2021Article
- Crosstalk of Hedgehog and mTORC1 Pathways.Cells · 2020Review
- Review
55 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Rheb G-protein plays critical roles in the TSC/Rheb/mTOR signaling pathway by activating mTORC1. The activation of mTORC1 by Rheb can be faithfully reproduced in vitro by using mTORC1 immunoprecipitated by the use of anti-raptor antibody from mammalian cells starved for nutrients. The low in vitro kinase activity against 4E-BP1 of this mTORC1 preparation is dramatically increased by the addition of recombinant Rheb. On the other hand, the addition of Rheb does not activate mTORC2 immunoprecipitated from mammalian cells by the use of anti-rictor antibody. The activation of mTORC1 is specific to Rheb, because other G-proteins such as KRas, RalA/B, and Cdc42 did not activate mTORC1. Both Rheb1 and Rheb2 activate mTORC1. In addition, the activation is dependent on the presence of bound GTP. We also find that the effector domain of Rheb is required for the mTORC1 activation. FKBP38, a recently proposed mediator of Rheb action, appears not to be involved in the Rheb-dependent activation of mTORC1 in vitro, because the preparation of mTORC1 that is devoid of FKBP38 is still activated by Rheb. The addition of Rheb results in a significant increase of binding of the substrate protein 4E-BP1 to mTORC1. PRAS40, a TOR signaling (TOS) motif-containing protein that competes with the binding of 4EBP1 to mTORC1, inhibits Rheb-induced activation of mTORC1. A preparation of mTORC1 that is devoid of raptor is not activated by Rheb. Rheb does not induce autophosphorylation of mTOR. These results suggest that Rheb induces alteration in the binding of 4E-BP1 with mTORC1 to regulate mTORC1 activation.
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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.