ArticleThe Journal of biological chemistry2008
A novel Epac-Rap-PP2A signaling module controls cAMP-dependent Akt regulation.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 58 citations in OpenAlex.
- Resveratrol Induces Myotube Development by Altering Circadian Metabolism via the SIRT1-AMPK-PP2A Axis.Cells · 2024Article
- Resveratrol Induces the Fasting State and Alters Circadian Metabolism in Hepatocytes.Plant foods for human nutrition (Dordrecht, Netherlands) · 2022Article
- Chrysin Ameliorates Cyclosporine-A-Induced Renal Fibrosis by Inhibiting TGF-βInternational journal of molecular sciences · 2021Article
- TGF-β1 induces N-cadherin expression by upregulating Sox9 expression and promoting its nuclear translocation in human oral squamous cell carcinoma cells.Oncology letters · 2020Article
- Dynamic Phosphorylation and Dephosphorylation of Cyclase-Associated Protein 1 by Antagonistic Signaling through Cyclin-Dependent Kinase 5 and cAMP Are Critical for the Protein Functions in Actin Filament Disassembly and Cell Adhesion.Molecular and cellular biology · 2020Article
- Article
- Phospho-substrate profiling of Epac-dependent protein kinase C activity.Molecular and cellular biochemistry · 2019Article
- G2A Protects Mice against Sepsis by Modulating Kupffer Cell Activation: Cooperativity with Adenosine Receptor 2b.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Dual TORCs driven and B56 orchestrated signaling network guides eukaryotic cell migration.BMB reports · 2017Article
- cAMP signaling increases histone deacetylase 8 expression via the Epac2-Rap1A-Akt pathway in H1299 lung cancer cells.Experimental & molecular medicine · 2017Article
- Regulating Axonal Responses to Injury: The Intersection between Signaling Pathways Involved in Axon Myelination and The Inhibition of Axon Regeneration.Frontiers in molecular neuroscience · 2016Review
- Neuroprotective role of prostaglandin PGE2 EP2 receptor in hemin-mediated toxicity.Neurotoxicology · 2015Article
- Switch in signaling control of mTORC1 activity after oncoprotein expression in thyroid cancer cell lines.The Journal of clinical endocrinology and metabolism · 2014Article
- Article
- Lipid biology of breast cancer.Biochimica et biophysica acta · 2013Review
- Dissecting molecular events in thyroid neoplasia provides evidence for distinct evolution of follicular thyroid adenoma and carcinoma.The American journal of pathology · 2011Article
- cAMP inhibits mammalian target of rapamycin complex-1 and -2 (mTORC1 and 2) by promoting complex dissociation and inhibiting mTOR kinase activity.Cellular signalling · 2011Article
- Identification of a novel TGFβ/PKA signaling transduceome in mediating control of cell survival and metastasis in colon cancer.PloS one · 2011Article
- Grb-2-associated binder 1 (Gab1) regulates postnatal ischemic and VEGF-induced angiogenesis through the protein kinase A-endothelial NOS pathway.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Rap1b has been implicated in the transduction of the cAMP mitogenic signal. It is phosphorylated and activated by cAMP, and its expression in models where cAMP is mitogenic leads to proliferation and tumorigenesis. Akt is a likely downstream effector of cAMP-Rap1 action. cAMP elevation induced a rapid and transient Akt inhibition that required activated and phosphorylated Rap1b. However, the mechanism(s) by which cAMP-Rap regulates Akt remains unclear. Here we show that (i) upstream regulators, PIK and PDK1, are not the target(s) of the cAMP inhibitory action; (ii) constitutively active Akt and calyculin A-stimulated Akt are resistant to cAMP inhibition, suggesting the action of a phosphatase; (iii) cAMP increases the rate of Akt dephosphorylation, directly implicating an Akt-phosphatase; (iv) Epac- and protein kinase A (PKA)-specific analogs synergistically inhibit Akt, indicating the involvement of both cAMP-dependent effector pathways; (v) H89 and dominant negative Epac 279E block cAMP-inhibitory action; (vi) Epac associates in a complex with Akt and PP2A, and the associated-phosphatase activity is positively modulated by cAMP in a PKA- and Rap1-dependent manner; (vii) like its action on Akt inhibition, PKA- and Epac-specific analogs synergistically activate Epac-associated PP2A; and (viii) dominant negative PP2A blocks cAMP-inhibitory action. Thus, we uncovered a novel cAMP-Epac/PKA-Rap1b-PP2A signaling module involved in Akt regulation that may represent a physiological event in the process of cAMP stimulation of thyroid mitogenesis.
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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.