ArticleOncotarget2017
Association of mSin1 with mTORC2 Ras and Akt reveals a crucial domain on mSin1 involved in Akt phosphorylation.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Phytochemicals regulate cancer metabolism through modulation of the AMPK/PGC-1α signaling pathway.BMC cancer · 2024Pooled it
- Development of a SIN1 Targeting Inhibitor as a Novel Therapeutic Approach for the Treatment of Malignancies.Molecular cancer therapeutics · 2026Article
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Targeted suppression of mTORC2 reduces seizures across models of epilepsy.Nature communications · 2023Article
- Modulating mTOR Signaling as a Promising Therapeutic Strategy for Atherosclerosis.International journal of molecular sciences · 2022Review
- Regulation and metabolic functions of mTORC1 and mTORC2.Physiological reviews · 2021Review
- Ras, PI3K and mTORC2 - three's a crowd?Journal of cell science · 2020Review
- mTORC2 Is Involved in the Induction of RSK Phosphorylation by Serum or Nutrient Starvation.Cells · 2020Article
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- Review
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- Palmitic acid-induced lipotoxicity promotes a novel interplay between Akt-mTOR, IRS-1, and FFAR1 signaling in pancreatic β-cells.Biological research · 2019Article
- Rab5 GTPases are required for optimal TORC2 function.The Journal of cell biology · 2019Article
- The Functional Proximal Proteome of Oncogenic Ras Includes mTORC2.Molecular cell · 2019Article
- c-Jun N-terminal kinase (JNK)-mediated induction of mSin1 expression and mTORC2 activation in mesenchymal cells during fibrosis.The Journal of biological chemistry · 2018Article
- Protective effect of docosahexaenoic acid on lipotoxicity-mediated cell death in Schwann cells: Implication of PI3K/AKT and mTORC2 pathways.Brain and behavior · 2018Article
- The role of mTOR-mediated signals during haemopoiesis and lineage commitment.Biochemical Society transactions · 2018Review
- Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases.Oxidative medicine and cellular longevity · 2018Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mSin1 is a unique component within the mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which is responsible for cellular morphology and glucose metabolism. The association between mSin1 and other mTORC2 components, as well as their functions, has been explored previously; nevertheless, the mapping of the various binding domains of the components is lacking. Based on an evolutionary analysis of the gene, we constructed various fragments and truncated-forms of mSin1. We characterized the individual binding sites of mSin1 with its various partners, including mTOR, Rictor, Ras, and Akt. mTOR and Rictor bind to the amino acid (aa) 100-240 region of mSin1, which is different to the Ras binding site, the aa 260-460 region. A reciprocal examination found that mSin1 associated with the aa 2148-2300 region of mTOR, which is within the kinase domain, and with the carboxyl terminus of Rictor. Interestingly, Akt was found to associate with mSin1 in a region that slightly overlapped with the mTOR/Rictor complex binding site, namely aa 220-260. When only the Akt binding site was deleted from mSin1, phosphorylation of Akt S473 was greatly reduced. Furthermore, the association between Akt and mTOR can be regulated by serum, insulin and LY294002, but not by rapamycin or MAPK kinase inhibitors. Taken together, mSin1 would seem to act as a hub that allows mTORC2 to phosphorylate Akt S473. Our findings should facilitate future proteomic and crystallographic studies, help the development of dominant inhibitors and promote the identification of new drug targets.
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