ArticleThe Journal of biological chemistry2011
Raptor and Rheb negatively regulate skeletal myogenesis through suppression of insulin receptor substrate 1 (IRS1).
Article in The Journal of biological chemistry, 2011. 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, 38 citations in OpenAlex.
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- A non-translational role of threonyl-tRNA synthetase in regulating JNK signaling during myogenic differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Tissue-specific role and associated downstream signaling pathways of adiponectin.Cell & bioscience · 2021Review
- Skeletal Muscle Transcriptome Analysis of Hanzhong Ma Duck at Different Growth Stages Using RNA-Seq.Biomolecules · 2021Article
- Nontranslational function of leucyl-tRNA synthetase regulates myogenic differentiation and skeletal muscle regeneration.The Journal of clinical investigation · 2019Article
- Lack of muscle mTOR kinase activity causes early onset myopathy and compromises whole-body homeostasis.Journal of cachexia, sarcopenia and muscle · 2019Article
- Effects of rapamycin on growth hormone receptor knockout mice.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Combined QTL and Genome Scan Analyses With the Help of 2b-RAD Identify Growth-Associated Genetic Markers in a New Fast-Growing Carp Strain.Frontiers in genetics · 2018Article
- Depletion of the mRNA translation initiation inhibitor, programmed cell death protein 4 (PDCD4), impairs L6 myotube formation.Physiological reports · 2017Article
- Differentiation capacities of skeletal muscle satellite cells in Lantang and Landrace piglets.Oncotarget · 2017Article
- Heterogeneous nuclear ribonucleoprotein M associates with mTORC2 and regulates muscle differentiation.Scientific reports · 2017Article
- Negative regulation of initial steps in skeletal myogenesis by mTOR and other kinases.Scientific reports · 2016Article
- From Nutrient to MicroRNA: a Novel Insight into Cell Signaling Involved in Skeletal Muscle Development and Disease.International journal of biological sciences · 2016Review
- 4E-BPs Control Fat Storage by Regulating the Expression of Egr1 and ATGL.The Journal of biological chemistry · 2015Article
- Gene coexpression networks reveal key drivers of phenotypic divergence in porcine muscle.BMC genomics · 2015Article
- Role of the mTORC1 complex in satellite cell activation by RNA-induced mitochondrial restoration: dual control of cyclin D1 through microRNAs.Molecular and cellular biology · 2014Article
- Distinct amino acid-sensing mTOR pathways regulate skeletal myogenesis.Molecular biology of the cell · 2013Article
- XPLN is an endogenous inhibitor of mTORC2.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Late-life enalapril administration induces nitric oxide-dependent and independent metabolic adaptations in the rat skeletal muscle.Age (Dordrecht, Netherlands) · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The mammalian target of rapamycin (mTOR) is essential for skeletal myogenesis through controlling distinct cellular pathways. The importance of the canonical mTOR complex 1 signaling components, including raptor, S6K1, and Rheb, had been suggested in muscle maintenance, growth, and metabolism. However, the role of those components in myogenic differentiation is not entirely clear. In this study we have investigated the functions of raptor, S6K1, and Rheb in the differentiation of C2C12 mouse myoblasts. We find that although mTOR knockdown severely impairs myogenic differentiation as expected, the knockdown of raptor, as well as Rheb, enhances differentiation. Consistent with a negative role for these proteins in myogenesis, overexpression of raptor or Rheb inhibits C2C12 differentiation. On the other hand, neither knockdown nor overexpression of S6K1 has any effect. Moreover, the enhanced differentiation elicited by raptor or Rheb knockdown is accompanied by increased Akt activation, elevated IRS1 protein levels, and decreased Ser-307 (human Ser-312) phosphorylation on IRS1. Finally, IRS1 knockdown eliminated the enhancement in differentiation elicited by raptor or Rheb knockdown, suggesting that IRS1 is a critical mediator of the myogenic functions of raptor and Rheb. In conclusion, the Rheb-mTOR/raptor pathway negatively regulates myogenic differentiation by suppressing IRS1-PI3K-Akt signaling. These findings underscore the versatility of mTOR signaling in biological regulations and implicate the existence of novel mTOR complexes and/or signaling mechanism in skeletal myogenesis.
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Registered trials
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