ArticleMolecular endocrinology (Baltimore, Md.)2010
cAMP-dependent activation of mammalian target of rapamycin (mTOR) in thyroid cells. Implication in mitogenesis and activation of CDK4.
Article in Molecular endocrinology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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
38 citing papers in PubMed, 68 citations in OpenAlex.
- Peptide hormones and bile acids shaping immune tolerance of the liver: implications and applications.Protein & cell · 2026Review
- Advances in Adipose Tissue Biology.Endocrine reviews · 2026Review
- Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Defining theThyroid : official journal of the American Thyroid Association · 2024Article
- Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR.bioRxiv : the preprint server for biology · 2024Article
- Regulation of mTOR Signaling: Emerging Role of Cyclic Nucleotide-Dependent Protein Kinases and Implications for Cardiometabolic Disease.International journal of molecular sciences · 2023Review
- Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma.Nature reviews. Urology · 2022Review
- Review
- Crosstalk between beta-adrenergic and insulin signaling mediates mechanistic target of rapamycin hyperactivation in liver of high-fat diet-fed male mice.Physiological reports · 2021Article
- Enhanced insulin signalling ameliorates C9orf72 hexanucleotide repeat expansion toxicity ineLife · 2021Article
- Regulation of mTORC1 by Upstream Stimuli.Genes · 2020Review
- Hormonal Regulation of Autophagy in Thyroid PCCL3 Cells and the Thyroids of Male Mice.Journal of the Endocrine Society · 2020Article
- Loss of DP1 Aggravates Vascular Remodeling in Pulmonary Arterial Hypertension via mTORC1 Signaling.American journal of respiratory and critical care medicine · 2020Article
- Thyroid Nodules in Type 2 Diabetes Mellitus.Current medical science · 2019Article
- Article
- Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD-1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway.Oncology letters · 2019Article
- Autophagy in bone homeostasis and the onset of osteoporosis.Bone research · 2019Article
- E2F1 promotes hepatic gluconeogenesis and contributes to hyperglycemia during diabetes.Molecular metabolism · 2018Article
- Effect of beta-agonists on LAM progression and treatment.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- CDK4 phosphorylation status and a linked gene expression profile predict sensitivity to palbociclib.EMBO molecular medicine · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
How cAMP-dependent protein kinases [protein kinase A (PKA)] transduce the mitogenic stimulus elicited by TSH in thyroid cells to late activation of cyclin D3-cyclin-dependent kinase 4 (CDK4) remains enigmatic. Here we show in PC Cl3 rat thyroid cells that TSH/cAMP, like insulin, activates the mammalian target of rapamycin (mTOR)-raptor complex (mTORC1) leading to phosphorylation of S6K1 and 4E-BP1. mTORC1-dependent S6K1 phosphorylation in response to both insulin and cAMP required amino acids, whereas inhibition of AMP-activated protein kinase and glycogen synthase kinase 3 enhanced insulin but not cAMP effects. Unlike insulin, TSH/cAMP did not activate protein kinase B or induce tuberous sclerosis complex 2 phosphorylation at T1462 and Y1571. However, like insulin, TSH/cAMP produced a stable increase in mTORC1 kinase activity that was associated with augmented 4E-BP1 binding to raptor. This could be caused in part by T246 phosphorylation of PRAS40, which was found as an in vitro substrate of PKA. Both in PC Cl3 cells and primary dog thyrocytes, rapamycin inhibited DNA synthesis and retinoblastoma protein phosphorylation induced by TSH and insulin. Although rapamycin reduced cyclin D3 accumulation, the abundance of cyclin D3-CDK4 complexes was not affected. However, rapamycin inhibited the activity of these complexes by decreasing the TSH and insulin-mediated stimulation of activating T172 phosphorylation of CDK4. We propose that mTORC1 activation by TSH, at least in part through PKA-dependent phosphorylation of PRAS40, crucially contributes to mediate cAMP-dependent mitogenesis by regulating CDK4 T172-phosphorylation.
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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.