ArticleCellular signalling2011
cAMP inhibits mammalian target of rapamycin complex-1 and -2 (mTORC1 and 2) by promoting complex dissociation and inhibiting mTOR kinase activity.
Article in Cellular signalling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 69 citations in OpenAlex.
- Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1.Nature communications · 2026Article
- Peptide hormones and bile acids shaping immune tolerance of the liver: implications and applications.Protein & cell · 2026Review
- Functional Role of Fatty Acid Synthase for Signal Transduction in Core-Binding Factor Acute Myeloid Leukemia with an Activating c-Kit Mutation.Biomedicines · 2025Article
- 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
- Drug Treatments for Neurodevelopmental Disorders: Targeting Signaling Pathways and Homeostasis.Current neurology and neuroscience reports · 2024Review
- Acidity suppresses CD8 + T-cell function by perturbing IL-2, mTORC1, and c-Myc signaling.The EMBO journal · 2024Article
- Phosphodiesterase Inhibition to Sensitize Non-Small-Cell Lung Cancer to Pemetrexed: A Double-Edged Strategy.Cancers · 2024Article
- Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR.bioRxiv : the preprint server for biology · 2024Article
- Dietary salt promotes cognition impairment through GLP-1R/mTOR/p70S6K signaling pathway.Scientific reports · 2024Article
- mGluR7 allosteric modulator AMN082 corrects protein synthesis and pathological phenotypes in FXS.EMBO molecular medicine · 2024Article
- Leucine and arginine enhance milk fat and milk protein synthesis via the CaSR/GEuropean journal of nutrition · 2023Article
- MAGED2 Depletion Promotes Stress-Induced Autophagy by Impairing the cAMP/PKA Pathway.International journal of molecular sciences · 2023Article
- Regulation of mTOR Signaling: Emerging Role of Cyclic Nucleotide-Dependent Protein Kinases and Implications for Cardiometabolic Disease.International journal of molecular sciences · 2023Review
- Upregulation of acid ceramidase contributes to tumor progression in tuberous sclerosis complex.JCI insight · 2023Article
- Crosstalk between the mTOR pathway and primary cilia in human diseases.Current topics in developmental biology · 2023Review
- Sodium acetate regulates milk fat synthesis through the activation of GPR41/GPR43 signaling pathway.Frontiers in nutrition · 2023Article
- Review
- In Vitro Effects of Papaverine on Cell Migration and Vascular Endothelial Growth Factor in Cancer Cell Lines.International journal of molecular sciences · 2022Article
- Theophylline: Old Drug in a New Light, Application in COVID-19 through Computational Studies.International journal of molecular sciences · 2022Review
- Stress hormone signalling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner via mTORC1 and the circadian gene PER1.Immunology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
cAMP and mTOR signalling pathways control a number of critical cellular processes including metabolism, protein synthesis, proliferation and cell survival and therefore understanding the signalling events which integrate these two signalling pathways is of particular interest. In this study, we show that the pharmacological elevation of [cAMP](i) in mouse embryonic fibroblasts (MEFs) and human embryonic kidney 293 (HEK293) cells inhibits mTORC1 activation via a PKA-dependent mechanism. Although the inhibitory effect of cAMP on mTOR could be mediated by impinging on signalling cascades (i.e. PKB, MAPK and AMPK) that inhibit TSC1/2, an upstream negative regulator of mTORC1, we show that cAMP inhibits mTORC1 in TSC2 knockout (TSC2(-/-)) MEFs. We also show that cAMP inhibits insulin and amino acid-stimulated mTORC1 activation independently of Rheb, Rag GTPases, TSC2, PKB, MAPK and AMPK, indicating that cAMP may act independently of known regulatory inputs into mTOR. Moreover, we show that the prolonged elevation in [cAMP](i) can also inhibit mTORC2. We provide evidence that this cAMP-dependent inhibition of mTORC1/2 is caused by the dissociation of mTORC1 and 2 and a reduction in mTOR catalytic activity, as determined by its auto-phosphorylation on Ser2481. Taken together, these results provide an important insight into how cAMP signals to mTOR and down-regulates its activity, which may lead to the identification of novel drug targets to inhibit mTOR that could be used for the treatment and prevention of human diseases such as cancer.
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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.