ArticleMolecular and cellular biology2010
Cyclic AMP controls mTOR through regulation of the dynamic interaction between Rheb and phosphodiesterase 4D.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
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- Rescue of hippocampal synaptic plasticity and memory performance by Fingolimod (FTY720) in APP/PS1 model of Alzheimer's disease is accompanied by correction in metabolism of sphingolipids, polyamines, and phospholipid saturation composition.bioRxiv : the preprint server for biology · 2025Article
- mTORC1 hyperactivation and resultant suppression of macroautophagy contribute to the induction of cardiomyocyte necroptosis by catecholamine surges.Physiological reports · 2024Article
- mGluR7 allosteric modulator AMN082 corrects protein synthesis and pathological phenotypes in FXS.EMBO molecular medicine · 2024Article
- Inhibition of autophagy and induction of glioblastoma cell death by NEO214, a perillyl alcohol-rolipram conjugate.Autophagy · 2023Article
- Regulation of mTOR Signaling: Emerging Role of Cyclic Nucleotide-Dependent Protein Kinases and Implications for Cardiometabolic Disease.International journal of molecular sciences · 2023Review
- Mechanisms of Male Reproductive Toxicity of Polybrominated Diphenyl Ethers.International journal of molecular sciences · 2022Review
- Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2.eLife · 2022Article
- Glucagon transiently stimulates mTORC1 by activation of an EPAC/Rap1 signaling axis.Cellular signalling · 2021Article
- 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
- The imbalance of PGD2-DPs pathway is involved in the type 2 diabetes brain injury by regulating autophagy.International journal of biological sciences · 2021Article
- The mammalian target of rapamycin (mTOR) kinase mediates haloperidol-induced cataleptic behavior.Translational psychiatry · 2020Article
- Regulation of mTORC1 by Upstream Stimuli.Genes · 2020Review
- A Novel PDE4D Inhibitor BPN14770 Reverses Scopolamine-Induced Cognitive Deficits via cAMP/SIRT1/Akt/Bcl-2 Pathway.Frontiers in cell and developmental biology · 2020Article
- Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8Journal for immunotherapy of cancer · 2019Article
- Integrin α5β1 regulates PP2A complex assembly through PDE4D in atherosclerosis.The Journal of clinical investigation · 2019Article
- Article
- Farnesylation-defective Rheb Increases Axonal Length Independently of mTORC1 Activity in Embryonic Primary Neurons.Experimental neurobiology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
The mammalian target of rapamycin complex 1 (mTORC1) is a molecular hub that regulates protein synthesis in response to a number of extracellular stimuli. Cyclic AMP (cAMP) is considered to be an important second messenger that controls mTOR; however, the signaling components of this pathway have not yet been elucidated. Here, we identify cAMP phosphodiesterase 4D (PDE4D) as a binding partner of Rheb that acts as a cAMP-specific negative regulator of mTORC1. Under basal conditions, PDE4D binds Rheb in a noncatalytic manner that does not require its cAMP-hydrolyzing activity and thereby inhibits the ability of Rheb to activate mTORC1. However, elevated cAMP levels disrupt the interaction of PDE4D with Rheb and increase the interaction between Rheb and mTOR. This enhanced Rheb-mTOR interaction induces the activation of mTORC1 and cap-dependent translation, a cellular function of mTORC1. Taken together, our results suggest a novel regulatory mechanism for mTORC1 in which the cAMP-determined dynamic interaction between Rheb and PDE4D provides a key, unique regulatory event. We also propose a new role for PDE4 as a molecular transducer for cAMP 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.