ArticleThe Journal of biological chemistry2011
The cAMP-responsive Rap1 guanine nucleotide exchange factor, Epac, induces smooth muscle relaxation by down-regulation of RhoA activity.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 100 citations in OpenAlex.
- Article
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- Sonoepigenetic Modification Mechanoprimes Early Osteogenic Commitment in Mesenchymal Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Respiratory Ciliary Beat Frequency in COPD: Balancing Oxidative Stress and Pharmacological Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Genome-wide association analysis reveals insights into the genetic architecture of mesenteric torsion in pigs.Scientific reports · 2025Article
- Glucagon-Like Peptide-1 Links Ingestion, Homeostasis, and the Heart.Comprehensive Physiology · 2025Review
- Cilostazol-inhibited RhoA/NF-κB signaling mitigates hippocampal inflammation and post-stroke depression.Frontiers in pharmacology · 2025Article
- α-Hederin promotes ferroptosis and reverses cisplatin chemoresistance in non-small cell lung cancer.Aging · 2024Article
- A low androgen state impairs erectile function by suppressingTranslational andrology and urology · 2023Article
- IgG immune complex-induced acute lung injury is ameliorated by cAMP via down-regulation of C/EBP- and AP-1-mediated transcriptions.Journal of inflammation (London, England) · 2023Article
- Allosteric modulator potentiates β2AR agonist-promoted bronchoprotection in asthma models.The Journal of clinical investigation · 2023Article
- Host Cell Rap1b mediates cAMP-dependent invasion by Trypanosoma cruzi.PLoS neglected tropical diseases · 2023Article
- Perspectives of PDE inhibitor on treating idiopathic pulmonary fibrosis.Frontiers in pharmacology · 2023Review
- A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility.Cell · 2022Article
- cAMP and voltage modulate rat auditory mechanotransduction by decreasing the stiffness of gating springs.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- RhoA: a dubious molecule in cardiac pathophysiology.Journal of biomedical science · 2021Review
- The Potentially Therapeutic Role of EPAC in Curbing the Process of Idiopathic Pulmonary Fibrosis via Differential Cellular Pathways.Journal of inflammation research · 2021Article
- β-Adrenergic Receptors/Epac Signaling Increases the Size of the Readily Releasable Pool of Synaptic Vesicles Required for Parallel Fiber LTP.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Agonist activation of the small GTPase, RhoA, and its effector Rho kinase leads to down-regulation of smooth muscle (SM) myosin light chain phosphatase activity, an increase in myosin light chain (RLC(20)) phosphorylation and force. Cyclic nucleotides can reverse this process. We report a new mechanism of cAMP-mediated relaxation through Epac, a GTP exchange factor for the small GTPase Rap1 resulting in an increase in Rap1 activity and suppression of RhoA activity. An Epac-selective cAMP analog, 8-pCPT-2'-O-Me-cAMP ("007"), significantly reduced agonist-induced contractile force, RLC(20), and myosin light chain phosphatase phosphorylation in both intact and permeabilized vascular, gut, and airway SMs independently of PKA and PKG. The vasodilator PGI(2) analog, cicaprost, increased Rap1 activity and decreased RhoA activity in intact SMs. Forskolin, phosphodiesterase inhibitor isobutylmethylxanthine, and isoproterenol also significantly increased Rap1-GTP in rat aortic SM cells. The PKA inhibitor H89 was without effect on the 007-induced increase in Rap1-GTP. Lysophosphatidic acid-induced RhoA activity was reduced by treatment with 007 in WT but not Rap1B null fibroblasts, consistent with Epac signaling through Rap1B to down-regulate RhoA activity. Isoproterenol-induced increase in Rap1 activity was inhibited by silencing Epac1 in rat aortic SM cells. Evidence is presented that cooperative cAMP activation of PKA and Epac contribute to relaxation of SM. Our findings demonstrate a cAMP-mediated signaling mechanism whereby activation of Epac results in a PKA-independent, Rap1-dependent Ca(2+) desensitization of force in SM through down-regulation of RhoA activity. Cyclic AMP inhibition of RhoA is mediated through activation of both Epac and PKA.
Indexed as
Identifiers
What OpenQuestion holds
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.