ArticleThe Journal of biological chemistry2017
Identification of mechanically regulated phosphorylation sites on tuberin (TSC2) that control mechanistic target of rapamycin (mTOR) signaling.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Evolution of growth factor signaling to the TSC complex to regulate mTORC1.Science signaling · 2025Review
- Identification of a resistance-exercise-specific signalling pathway that drives skeletal muscle growth.Nature metabolism · 2025Article
- Mechanically sensitive MAPK signalling mediates resistance exercise-induced muscle growth.Nature metabolism · 2025Article
- Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions.Physiological reviews · 2023Review
- The skeletal muscle fiber periphery: A nexus of mTOR-related anabolism.Sports medicine and health science · 2023Review
- microRNAs profiling of small extracellular vesicles from midbrain tissue of Parkinson's disease.Frontiers in molecular neuroscience · 2023Article
- Alcohol, Resistance Exercise, and mTOR Pathway Signaling: An Evidence-Based Narrative Review.Biomolecules · 2022Review
- CORP: Gene delivery into murine skeletal muscle using in vivo electroporation.Journal of applied physiology (Bethesda, Md. : 1985) · 2022Review
- Long-term administration of sirolimus does not affect the physical development of children with tuberous sclerosis complex.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022Article
- Review
- Mechanisms of exercise as a preventative measure to muscle wasting.American journal of physiology. Cell physiology · 2021Review
- A clinically relevant decrease in contractile force differentially regulates control of glucocorticoid receptor translocation in mouse skeletal muscle.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- Integrated Genomic Profiling and Drug Screening of Patient-Derived Cultures Identifies Individualized Copy Number-Dependent Susceptibilities Involving PI3K Pathway and 17q Genes in Neuroblastoma.Frontiers in oncology · 2021Article
- Molecular Events Occurring in Lipophagy and Its Regulation inFrontiers in microbiology · 2021Review
- Mechanical Regulation of Protein Translation in the Cardiovascular System.Frontiers in cell and developmental biology · 2020Review
- Molecular regulation of human skeletal muscle protein synthesis in response to exercise and nutrients: a compass for overcoming age-related anabolic resistance.American journal of physiology. Cell physiology · 2019Review
- Chronic shisha exposure alters phosphoproteome of oral keratinocytes.Journal of cell communication and signaling · 2019Article
- Enzyme-Aided Extraction of Fucoidan by AMG Augments the Functionality of EPCs through Regulation of the AKT/Rheb Signaling Pathway.Marine drugs · 2019Article
- Normal Ribosomal Biogenesis but Shortened Protein Synthetic Response to Acute Eccentric Resistance Exercise in Old Skeletal Muscle.Frontiers in physiology · 2018Article
- Do metabolites that are produced during resistance exercise enhance muscle hypertrophy?European journal of applied physiology · 2017Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Mechanistic target of rapamycin (mTOR) signaling is necessary to generate a mechanically induced increase in skeletal muscle mass, but the mechanism(s) through which mechanical stimuli regulate mTOR signaling remain poorly defined. Recent studies have suggested that Ras homologue enriched in brain (Rheb), a direct activator of mTOR, and its inhibitor, the GTPase-activating protein tuberin (TSC2), may play a role in this pathway. To address this possibility, we generated inducible and skeletal muscle-specific knock-out mice for Rheb (iRhebKO) and TSC2 (iTSC2KO) and mechanically stimulated muscles from these mice with eccentric contractions (EC). As expected, the knock-out of TSC2 led to an elevation in the basal level of mTOR signaling. Moreover, we found that the magnitude of the EC-induced activation of mTOR signaling was significantly blunted in muscles from both inducible and skeletal muscle-specific knock-out mice for Rheb and iTSC2KO mice. Using mass spectrometry, we identified six sites on TSC2 whose phosphorylation was significantly altered by the EC treatment. Employing a transient transfection-based approach to rescue TSC2 function in muscles of the iTSC2KO mice, we demonstrated that these phosphorylation sites are required for the role that TSC2 plays in the EC-induced activation of mTOR signaling. Importantly, however, these phosphorylation sites were not required for an insulin-induced activation of mTOR signaling. As such, our results not only establish a critical role for Rheb and TSC2 in the mechanical activation of mTOR signaling, but they also expose the existence of a previously unknown branch of signaling events that can regulate the TSC2/mTOR pathway.
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