ArticleProceedings of the National Academy of Sciences of the United States of America2015
A CaMKII/PDE4D negative feedback regulates cAMP signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Integrative functional analysis of super enhancer SNPs for coronary artery disease.Journal of human genetics · 2018Pooled it
- Posttranslational modifications of phosphodiesterase type 4 enzymes represent novel points for therapeutic targeting.The FEBS journal · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Investigation of the effects of catharanthine and Q10 on Nrf2 and its association with MMP-9, MRP1, and Bcl-2 and apoptosis in a model of hepatocellular carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- PDE4D mediates impaired β-adrenergic receptor signalling in the sinoatrial node in mice with hypertensive heart disease.Cardiovascular research · 2023Article
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Arrestin-dependent nuclear export of phosphodiesterase 4D promotes GPCR-induced nuclear cAMP signaling required for learning and memory.Science signaling · 2023Article
- Chronotherapeutic neuroprotective effect of verapamil against lipopolysaccharide-induced neuroinflammation in mice through modulation of calcium-dependent genes.Molecular medicine (Cambridge, Mass.) · 2022Article
- A Modeling and Analysis Study Reveals That CaMKII in Synaptic Plasticity Is a Dominant Affecter in CaM Systems in a T286 Phosphorylation-Dependent Manner.Molecules (Basel, Switzerland) · 2022Article
- PDE4DIP in health and diseases.Cellular signalling · 2022Review
- Analysis of localized cAMP perturbations within a tissue reveal the effects of a local, dynamic gap junction state on ERK signaling.PLoS computational biology · 2022Article
- Epistatic interaction of PDE4DIP and DES mutations in familial atrial fibrillation with slow conduction.Human mutation · 2021Article
- Molecular Targets and Biological Functions of cAMP Signaling inBiomolecules · 2021Article
- Taurine-Mediated IDOL Contributes to Resolution of Streptococcus uberis Infection.Infection and immunity · 2021Article
- Biochemical evidence accumulates across neurons to drive a network-level eruption.Molecular cell · 2021Article
- CaMKIIδ Splice Variants in the Healthy and Diseased Heart.Frontiers in cell and developmental biology · 2021Review
- The CaMKII phosphorylation site Thr1604 in the CaChannels (Austin, Tex.) · 2020Article
- Theobromine alleviates diet-induced obesity in mice via phosphodiesterase-4 inhibition.European journal of nutrition · 2020Article
- Identification of Four Potential Biomarkers Associated With Coronary Artery Disease in Non-diabetic Patients by Gene Co-expression Network Analysis.Frontiers in genetics · 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
cAMP production and protein kinase A (PKA) are the most widely studied steps in β-adrenergic receptor (βAR) signaling in the heart; however, the multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is also activated in response to βAR stimulation and is involved in the regulation of cardiac excitation-contraction coupling. Its activity and expression are increased during cardiac hypertrophy, in heart failure, and under conditions that promote arrhythmias both in animal models and in the human heart, underscoring the clinical relevance of CaMKII in cardiac pathophysiology. Both CaMKII and PKA phosphorylate a number of protein targets critical for Ca(2+) handling and contraction with similar, but not always identical, functional consequences. How these two pathways communicate with each other remains incompletely understood, however. To maintain homeostasis, cyclic nucleotide levels are regulated by phosphodiesterases (PDEs), with PDE4s predominantly responsible for cAMP degradation in the rodent heart. Here we have reassessed the interaction between cAMP/PKA and Ca(2+)/CaMKII signaling. We demonstrate that CaMKII activity constrains basal and βAR-activated cAMP levels. Moreover, we show that these effects are mediated, at least in part, by CaMKII regulation of PDE4D. This regulation establishes a negative feedback loop necessary to maintain cAMP/CaMKII homeostasis, revealing a previously unidentified function for PDE4D as a critical integrator of cAMP/PKA and Ca(2+)/CaMKII signaling.
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.