ArticleCell research2016
mTORC2 promotes type I insulin-like growth factor receptor and insulin receptor activation through the tyrosine kinase activity of mTOR.
Article in Cell research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 2 syntheses or guidelines pooled it, 142 citations in OpenAlex.
- Tools for investigating O-GlcNAc in signaling and other fundamental biological pathways.The Journal of biological chemistry · 2024Pooled it
- Dairy Products: Is There an Impact on Promotion of Prostate Cancer? A Review of the Literature.Frontiers in nutrition · 2019Pooled it
- Evolving Landscape of Systemic Therapy for Hepatocellular Carcinoma: From Targeted Therapy and Combination Strategies to Emerging Therapies.Biomedicines · 2026Review
- Dental Pulp Stem Cell-Derived Intracellular Vesicles Inhibit OSCC by Delivering PTEN to Suppress PI3K/AKT/mTOR Signalling Pathway.Cell proliferation · 2026Article
- YTHDF3 Mediates the Occurrence and Development of Breast Cancer by Regulating Glycolysis Through the mTOR-HIF1α-LHDA Axis.Journal of cellular and molecular medicine · 2026Article
- Graph Neural Networks Model Based on Atomic Hybridization for Predicting Drug Targets.Journal of chemical information and modeling · 2026Article
- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- PI3K/AKT/mTOR axis in vascular malformations: from molecular insights to targeted clinical trials.Orphanet journal of rare diseases · 2025Review
- Graph Neural Networks Model Based on Atomic Hybridization for Predicting Drug Targets.bioRxiv : the preprint server for biology · 2025Article
- Application of Neurotrophic Factors as a Therapeutic Approach for Neurodegenerative Diseases.Experimental neurobiology · 2025Review
- Human iPSCs Derived MSCs-Secreted Exosomes Modulate Senescent Nucleus Pulposus Cells Induced Macrophage Polarization via Metabolic Reprogramming to Mitigate Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of Ephexin1 in translation and mTOR-targeted cancer therapy.Experimental & molecular medicine · 2025Article
- mTOR pathway targeted inhibition via Rapamycin-loaded PLGA nanoparticles for enhanced bladder cancer therapy.Scientific reports · 2025Article
- Lysionotin promoted apoptosis of hepatocellular carcinoma cells via inducing autophagy.Discover oncology · 2025Article
- Maternal Adiponectin Decreases Placenta Nutrient Transport in Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status.Signal transduction and targeted therapy · 2025Review
- The effect and mechanism of atorvastatin regulating PI3K-Akt-mTOR pathway on radiosensitivity of hepatocellular carcinoma cells.Toxicology research · 2025Article
- Molecular dynamics and experimental evaluation of piperine as a potential mTOR inhibitor in colon cancer cells.In silico pharmacology · 2025Article
- Targeting the PI3K/AKT/mTOR pathway in lung cancer: mechanisms and therapeutic targeting.Frontiers in pharmacology · 2025Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian target of rapamycin (mTOR) is a core component of raptor-mTOR (mTORC1) and rictor-mTOR (mTORC2) complexes that control diverse cellular processes. Both mTORC1 and mTORC2 regulate several elements downstream of type I insulin-like growth factor receptor (IGF-IR) and insulin receptor (InsR). However, it is unknown whether and how mTOR regulates IGF-IR and InsR themselves. Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR/InsR. Rapamycin induces the tyrosine phosphorylation and activation of IGF-IR/InsR, which is largely dependent on rictor and mTOR. Moreover, mTORC2 promotes ligand-induced activation of IGF-IR/InsR. IGF- and insulin-induced IGF-IR/InsR phosphorylation is significantly compromised in rictor-null cells. Insulin receptor substrate (IRS) directly interacts with SIN1 thereby recruiting mTORC2 to IGF-IR/InsR and promoting rapamycin- or ligand-induced phosphorylation of IGF-IR/InsR. mTOR exhibits tyrosine kinase activity towards the general tyrosine kinase substrate poly(Glu-Tyr) and IGF-IR/InsR. Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively. These effects are independent of the intrinsic kinase activity of IGF-IR/InsR, as determined by assays on kinase-dead IGF-IR/InsR mutants. While both rictor and mTOR immunoprecitates from rictor(+/+) MCF-10A cells exhibit tyrosine kinase activity towards IGF-IR and InsR, mTOR immunoprecipitates from rictor(-/-) MCF-10A cells do not induce IGF-IR and InsR phosphorylation. Phosphorylation-deficient mutation of residue Tyr1131 in IGF-IR or Tyr1146 in InsR abrogates the activation of IGF-IR/InsR by mTOR. Finally, overexpression of rictor promotes IGF-induced cell proliferation. Our work identifies mTOR as a dual-specificity kinase and clarifies how mTORC2 promotes IGF-IR/InsR 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.