ArticleThe Journal of biological chemistry2012
Unrestrained mammalian target of rapamycin complexes 1 and 2 increase expression of phosphatase and tensin homolog deleted on chromosome 10 to regulate phosphorylation of Akt kinase.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Traditional Chinese Medicine for Diabetic Sarcopenia: A Review and Its Related Mechanisms.Journal of diabetes research · 2026Review
- Association of triglyceride-glucose index with sarcopenia: NHANES 2011-2014.Frontiers in endocrinology · 2024Article
- Causal relationship between insulin resistance and sarcopenia.Diabetology & metabolic syndrome · 2023Review
- Rapamycin reduces neuronal mutant huntingtin aggregation and ameliorates locomotor performance inFrontiers in aging neuroscience · 2023Article
- Cholesterol-Lowering Drugs on Akt Signaling for Prevention of Tumorigenesis.Frontiers in genetics · 2021Review
- TGFβ acts through PDGFRβ to activate mTORC1 via the Akt/PRAS40 axis and causes glomerular mesangial cell hypertrophy and matrix protein expression.The Journal of biological chemistry · 2020Article
- Catalpol improves axonal outgrowth and reinnervation of injured sciatic nerve by activating Akt/mTOR pathway and regulating BDNF and PTEN expression.American journal of translational research · 2019Article
- Nox4 is a Target for Tuberin Deficiency Syndrome.Scientific reports · 2018Article
- Multiple lines of inhibitory feedback on AKT kinase in Schwann cells lacking TSC1/2 hint at distinct functions of mTORC1 and AKT in nerve development.Communicative & integrative biology · 2018Article
- Reciprocal regulation of miR-214 and PTEN by high glucose regulates renal glomerular mesangial and proximal tubular epithelial cell hypertrophy and matrix expansion.American journal of physiology. Cell physiology · 2017Article
- PDGF receptor-β uses Akt/mTORC1 signaling node to promote high glucose-induced renal proximal tubular cell collagen I (α2) expression.American journal of physiology. Renal physiology · 2017Article
- Inhibition of mTORC2 component RICTOR impairs tumor growth in pancreatic cancer models.Oncotarget · 2017Article
- MicroRNA-214 Reduces Insulin-like Growth Factor-1 (IGF-1) Receptor Expression and Downstream mTORC1 Signaling in Renal Carcinoma Cells.The Journal of biological chemistry · 2016Article
- Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2(-) Tumor Related to Lymphangioleiomyomatosis.The American journal of pathology · 2016Article
- Hydrophobic motif site-phosphorylated protein kinase CβII between mTORC2 and Akt regulates high glucose-induced mesangial cell hypertrophy.American journal of physiology. Cell physiology · 2016Article
- Beneficial Effects of Early mTORC1 Inhibition after Traumatic Brain Injury.Journal of neurotrauma · 2016Article
- microRNA-21-induced dissociation of PDCD4 from rictor contributes to Akt-IKKβ-mTORC1 axis to regulate renal cancer cell invasion.Experimental cell research · 2014Article
- Evaluation of apoptosis induction by concomitant inhibition of MEK, mTOR, and Bcl-2 in human acute myelogenous leukemia cells.Molecular cancer therapeutics · 2014Article
- A positive feedback loop involving Erk5 and Akt turns on mesangial cell proliferation in response to PDGF.American journal of physiology. Cell physiology · 2014Article
- Increased prevalence of eosinophilic gastrointestinal disorders in pediatric PTEN hamartoma tumor syndromes.Journal of pediatric gastroenterology and nutrition · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Tuberous sclerosis complex 2 (TSC2) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) function to block growth factor-induced mammalian target of rapamycin (mTOR) signaling and are mutated in autosomal dominant hamartoma syndromes. mTOR binds to a spectrum of common and different proteins to form TOR complex 1 (TORC1) and TORC2, which regulate cell growth, division, and metabolism. TSC2 deficiency induces constitutive activation of mTOR, leading to a state of insulin resistance due to a negative feedback regulation, resulting in reduced Akt phosphorylation. We have recently described an alternative mechanism showing that in TSC2 deficiency, enhanced PTEN expression contributes to reduced Akt phosphorylation. To explore the mechanism of PTEN regulation, we used rapamycin and constitutively active mTOR to show that TORC1 increases the expression of PTEN mRNA and protein. We found that in TSC2(-/-) mouse embryonic fibroblasts expression of a kinase-dead mutant of mTOR, which inhibits both TORC1 and TORC2, decreases the expression of PTEN via transcriptional mechanism. Furthermore, kinase-dead mTOR increased and decreased phosphorylation of Akt at catalytic loop site Thr-308 and hydrophobic motif site Ser-473, respectively. Moreover, inhibition of deregulated TORC1 in TSC2-null mouse embryonic fibroblasts or in 293 cells by down-regulation of raptor decreased the levels of the transcription factor Hif1α and blocked PTEN expression, resulting in enhanced phosphorylation of Akt at Thr-308 and Ser-473. Finally, knockdown of rictor or mSin1 attenuated the expression of Hif1α, which decreased transcription of PTEN. These results unravel a previously unrecognized cell-autonomous function of TORC1 and TORC2 in the up-regulation of PTEN, which prevents phosphorylation of Akt and may shield against the development of malignancy in TSC patients.
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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 Socratic graph.