ArticleCell communication and signaling : CCS2017
Unraveling the regulation of mTORC2 using logical modeling.
Article in Cell communication and signaling : CCS, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Modeling and analysis of the macronutrient signaling network in budding yeast.Molecular biology of the cell · 2021Article
- Interactions among mTORC, AMPK and SIRT: a computational model for cell energy balance and metabolism.Cell communication and signaling : CCS · 2021Article
- Review
- Modulating autophagy as a therapeutic strategy for the treatment of paediatric high-grade glioma.Brain pathology (Zurich, Switzerland) · 2019Review
- PI3K-AKT-mTOR and NFκB Pathways in Ovarian Cancer: Implications for Targeted Therapeutics.Cancers · 2019Review
- Akt Signaling in Macrophage Polarization, Survival, and Atherosclerosis.International journal of molecular sciences · 2019Review
- Farnesylation-defective Rheb Increases Axonal Length Independently of mTORC1 Activity in Embryonic Primary Neurons.Experimental neurobiology · 2019Article
- Recent Advances in the Systems Biology of Aging.Antioxidants & redox signaling · 2018Review
- Evaluating Uncertainty in Signaling Networks Using Logical Modeling.Frontiers in physiology · 2018Article
- Formal Modeling of mTOR Associated Biological Regulatory Network Reveals Novel Therapeutic Strategy for the Treatment of Cancer.Frontiers in physiology · 2017Article
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Authors and funding
3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe mammalian target of rapamycin (mTOR) is a regulator of cell proliferation, cell growth and apoptosis working through two distinct complexes: mTORC1 and mTORC2. Although much is known about the activation and inactivation of mTORC1, the processes controlling mTORC2 remain poorly characterized. Experimental and modeling studies have attempted to explain the regulation of mTORC2 but have yielded several conflicting hypotheses. More specifically, the Phosphoinositide 3-kinase (PI3K) pathway was shown to be involved in this process, but the identity of the kinase interacting with and regulating mTORC2 remains to be determined (Cybulski and Hall, Trends Biochem Sci 34:620-7, 2009).
methodWe performed a literature search and identified 5 published hypotheses describing mTORC2 regulation. Based on these hypotheses, we built logical models, not only for each single hypothesis but also for all combinations and possible mechanisms among them. Based on data provided by the original studies, a systematic analysis of all models was performed.
resultsWe were able to find models that account for experimental observations from every original study, but do not require all 5 hypotheses to be implemented. Surprisingly, all hypotheses were in agreement with all tested data gathered from the different studies and PI3K was identified as an essential regulator of mTORC2.
conclusionThe results and additional data suggest that more than one regulator is necessary to explain the behavior of mTORC2. Finally, this study proposes a new experiment to validate mTORC1 as second essential regulator.
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