ArticleCardiovascular research2014
Control of cytoplasmic and nuclear protein kinase A by phosphodiesterases and phosphatases in cardiac myocytes.
Article in Cardiovascular research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- GPCR-selective effects of endocytosis on cellular signaling through the cAMP/PKA cascade.The Journal of biological chemistry · 2026Article
- Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026Review
- Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Review
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Cyclic AMP induces reversible EPAC1 condensates that regulate histone transcription.Nature communications · 2023Article
- Multi-Omics Approach Profiling Metabolic Remodeling in Early Systolic Dysfunction and in Overt Systolic Heart Failure.International journal of molecular sciences · 2021Article
- Review
- Whole-Cell cAMP and PKA Activity are Epiphenomena, Nanodomain Signaling Matters.Physiology (Bethesda, Md.) · 2019Review
- PDE4 and mAKAPβ are nodal organizers of β2-ARs nuclear PKA signalling in cardiac myocytes.Cardiovascular research · 2018Article
- Phosphatases control PKA-dependent functional microdomains at the outer mitochondrial membrane.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Selective phosphodiesterase-2A inhibitor alleviates radicular inflammation and mechanical allodynia in non-compressive lumbar disc herniation rats.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2017Article
- Molecular inotropy mediated by cardiac miR-based PDE4D/PRKAR1α/phosphoprotein signaling.Scientific reports · 2016Article
- UCR1C is a novel activator of phosphodiesterase 4 (PDE4) long isoforms and attenuates cardiomyocyte hypertrophy.Cellular signalling · 2015Article
- Cardiac function is regulated by B56α-mediated targeting of protein phosphatase 2A (PP2A) to contractile relevant substrates.The Journal of biological chemistry · 2014Article
- Interventricular differences in β-adrenergic responses in the canine heart: role of phosphodiesterases.Journal of the American Heart Association · 2014Article
- The Popeye Domain Containing Genes and cAMP Signaling.Journal of cardiovascular development and disease · 2014Article
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
Abstract
aimsThe cAMP-dependent protein kinase (PKA) mediates β-adrenoceptor (β-AR) regulation of cardiac contraction and gene expression. Whereas PKA activity is well characterized in various subcellular compartments of adult cardiomyocytes, its regulation in the nucleus remains largely unknown. The aim of the present study was to compare the modalities of PKA regulation in the cytoplasm and nucleus of cardiomyocytes. METHODS AND
resultsCytoplasmic and nuclear cAMP and PKA activity were measured with targeted fluorescence resonance energy transfer probes in adult rat ventricular myocytes. β-AR stimulation with isoprenaline (Iso) led to fast cAMP elevation in both compartments, whereas PKA activity was fast in the cytoplasm but markedly slower in the nucleus. Iso was also more potent and efficient in activating cytoplasmic than nuclear PKA. Similar slow kinetics of nuclear PKA activation was observed upon adenylyl cyclase activation with L-858051 or phosphodiesterase (PDE) inhibition with 3-isobutyl-1-methylxantine. Consistently, pulse stimulation with Iso (15 s) maximally induced PKA and myosin-binding protein C phosphorylation in the cytoplasm, but marginally activated PKA and cAMP response element-binding protein phosphorylation in the nucleus. Inhibition of PDE4 or ablation of the Pde4d gene in mice prolonged cytoplasmic PKA activation and enhanced nuclear PKA responses. In the cytoplasm, phosphatase 1 (PP1) and 2A (PP2A) contributed to the termination of PKA responses, whereas only PP1 played a role in the nucleus.
conclusionOur study reveals a differential integration of cytoplasmic and nuclear PKA responses to β-AR stimulation in cardiac myocytes. This may have important implications in the physiological and pathological hypertrophic response to β-AR stimulation.
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Registered trials
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