ArticleMolecular and cellular biology2006
Exchange protein activated by cyclic AMP (Epac)-mediated induction of suppressor of cytokine signaling 3 (SOCS-3) in vascular endothelial cells.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 157 citations in OpenAlex.
- Peptide hormones and bile acids shaping immune tolerance of the liver: implications and applications.Protein & cell · 2026Review
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Inhibition of DYRK1B BY C81 impedes inflammatory processes in leukocytes by reducing STAT3 activity.Cellular and molecular life sciences : CMLS · 2025Article
- Therapeutic potential of peptidomimetics of suppressors of cytokine signaling (SOCS) proteins in rheumatic disorders.Frontiers in medicine · 2025Article
- Cyclic Adenosine Monophosphate in Cardiac and Sympathoadrenal GLP-1 Receptor Signaling: Focus on Anti-Inflammatory Effects.Pharmaceutics · 2024Review
- Obesity dysregulates the pulmonary antiviral immune response.Nature communications · 2023Article
- Usefulness of circulating EPAC1 as biomarkers of therapeutic response to GLP-1 receptor agonists.Acta diabetologica · 2022Article
- Protein interaction, cytotoxic, transcriptomic and proteomic responses to structurally distinct EPAC1 activators in HUVECs.Scientific reports · 2022Article
- The P2YCellular and molecular life sciences : CMLS · 2022Article
- Unraveling the role of Epac1-SOCS3 signaling in the development of neonatal-CRD-induced visceral hypersensitivity in rats.CNS neuroscience & therapeutics · 2022Article
- Epac activation ameliorates tubulointerstitial inflammation in diabetic nephropathy.Acta pharmacologica Sinica · 2022Article
- OvineFrontiers in veterinary science · 2022Article
- Review
- Rap1 in the VMH regulates glucose homeostasis.JCI insight · 2021Article
- The Potentially Therapeutic Role of EPAC in Curbing the Process of Idiopathic Pulmonary Fibrosis via Differential Cellular Pathways.Journal of inflammation research · 2021Article
- Overexpression of RAPGEF3 enhances the therapeutic effect of dezocine in treatment of neuropathic pain.Genetics and molecular biology · 2021Article
- Activation of βArchives of pharmacal research · 2021Review
- Selective small-molecule EPAC activators.Biochemical Society transactions · 2019Review
- Genome-Wide Mapping Defines a Role for C/EBPβ and c-Jun in Non-Canonical Cyclic AMP Signalling.Cells · 2019Article
- Luciferase Reporter Mice forJournal of the Endocrine Society · 2019Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here, we demonstrate that elevation of intracellular cyclic AMP (cAMP) in vascular endothelial cells (ECs) by either a direct activator of adenylyl cyclase or endogenous cAMP-mobilizing G protein-coupled receptors inhibited the tyrosine phosphorylation of STAT proteins by an interleukin 6 (IL-6) receptor trans-signaling complex (soluble IL-6Ralpha/IL-6). This was associated with the induction of suppressor of cytokine signaling 3 (SOCS-3), a bona fide inhibitor in vivo of gp130, the signal-transducing component of the IL-6 receptor complex. Attenuation of SOCS-3 induction in either ECs or SOCS-3-null murine embryonic fibroblasts abolished the inhibitory effect of cAMP, whereas inhibition of SHP-2, another negative regulator of gp130, was without effect. Interestingly, the inhibition of STAT phosphorylation and SOCS-3 induction did not require cAMP-dependent protein kinase activity but could be recapitulated upon selective activation of the alternative cAMP sensor Epac, a guanine nucleotide exchange factor for Rap1. Consistent with this hypothesis, small interfering RNA-mediated knockdown of Epac1 was sufficient to attenuate both cAMP-mediated SOCS-3 induction and inhibition of STAT phosphorylation, suggesting that Epac activation is both necessary and sufficient to observe these effects. Together, these data argue for the existence of a novel cAMP/Epac/Rap1/SOCS-3 pathway for limiting IL-6 receptor signaling in ECs and illuminate a new mechanism by which cAMP may mediate its potent anti-inflammatory effects.
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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.