ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2).
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 95 citations in OpenAlex.
- The mTORC2 subunit RICTOR drives breast cancer progression by promoting ganglioside biosynthesis through transcriptional and epigenetic mechanisms.PLoS biology · 2025Article
- Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes.Experimental & molecular medicine · 2025Article
- Inhibition of mTORC1 by rapamycin results in feedback activation of AktbioRxiv : the preprint server for biology · 2025Article
- RICTOR/mTORC2 downregulation in BRAFMolecular cancer · 2024Article
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Blazing a trail for the clinical use of rapamycin as a geroprotecTOR.GeroScience · 2023Article
- Hepatic mTORC2 Signaling Facilitates Acute Glucagon Receptor Enhancement of Insulin-Stimulated Glucose Homeostasis in Mice.Diabetes · 2022Article
- NAD/NAMPT and mTOR Pathways in Melanoma: Drivers of Drug Resistance and Prospective Therapeutic Targets.International journal of molecular sciences · 2022Review
- Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice.Aging cell · 2022Article
- Exercise increases phosphorylation of the putative mTORC2 activity readout NDRG1 in human skeletal muscle.American journal of physiology. Endocrinology and metabolism · 2022Article
- Dengue activates mTORC2 signaling to counteract apoptosis and maximize viral replication.Frontiers in cellular and infection microbiology · 2022Article
- Proteome Analysis of PC12 Cells Reveals Alterations in Translation Regulation and Actin Signaling Induced by Clozapine.Neurochemical research · 2021Article
- Programmed suppression of oxidative phosphorylation and mitochondrial function by gestational alcohol exposure correlate with widespread increases in H3K9me2 that do not suppress transcription.Epigenetics & chromatin · 2021Article
- Proteomic analysis of mitochondrial biogenesis in cardiomyocytes differentiated from human induced pluripotent stem cells.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Aging and Protein Kinases.Advances in experimental medicine and biology · 2021Article
- Article
- mTORC2 Signaling Is Necessary for Timely Liver Regeneration after Partial Hepatectomy.The American journal of pathology · 2020Article
- Next Generation Strategies for Geroprotection via mTORC1 Inhibition.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Review
- Hepatic stearoyl CoA desaturase 1 deficiency increases glucose uptake in adipose tissue partially through the PGC-1α-FGF21 axis in mice.The Journal of biological chemistry · 2019Article
- Fibroblast mTOR/PPARγ/HGF axis protects against tubular cell death and acute kidney injury.Cell death and differentiation · 2019Article
Corrections and comments
- Erratum issuedErratum.2021
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
The mechanistic target of rapamycin (mTOR) exists in two complexes that regulate diverse cellular processes. mTOR complex 1 (mTORC1), the canonical target of rapamycin, has been well studied, whereas the physiological role of mTORC2 remains relatively uncharacterized. In mice in which the mTORC2 component Rictor is deleted in liver [Rictor-knockout (RKO) mice], we used genomic and phosphoproteomic analyses to characterize the role of hepatic mTORC2 in vivo. Overnight food withdrawal followed by refeeding was used to activate mTOR signaling. Rapamycin was administered before refeeding to specify mTORC2-mediated events. Hepatic mTORC2 regulated a complex gene expression and post-translational network that affects intermediary metabolism, ribosomal biogenesis, and proteasomal biogenesis. Nearly all changes in genes related to intermediary metabolic regulation were replicated in cultured fetal hepatocytes, indicating a cell-autonomous effect of mTORC2 signaling. Phosphoproteomic profiling identified mTORC2-related signaling to 144 proteins, among which were metabolic enzymes and regulators. A reduction of p38 MAPK signaling in the RKO mice represents a link between our phosphoproteomic and gene expression results. We conclude that hepatic mTORC2 exerts a broad spectrum of biological effects under physiological conditions. Our findings provide a context for the development of targeted therapies to modulate mTORC2 signaling.
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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.