ArticleJournal of molecular and cellular cardiology2018
Compartmentalized cyclic nucleotides have opposing effects on regulation of hypertrophic phospholipase Cε signaling in cardiac myocytes.
Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- A framework to map cAMP signalling nanodomains: phosphodiesterase-centred phosphoproteome-interactome networks (pPINs) in cardiac myocytes.Journal of molecular endocrinology · 2026Review
- Phospholipase C epsilon 1 as a therapeutic target in cardiovascular diseases.Journal of advanced research · 2025Review
- Cryo-EM structure of phospholipase Cε defines N-terminal domains and their roles in activity.Communications biology · 2025Article
- RhoA allosterically activates phospholipase Cε via its EF hands.Communications biology · 2025Article
- Unique Role of Intracellular Perinuclear βCirculation · 2025Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cellular mechanisms underlying pituitary adenylate cyclase activating polypeptide-stimulated secretion in the adrenal medulla.Biochemical Society transactions · 2024Review
- Internalized β2-Adrenergic Receptors Oppose PLC-Dependent Hypertrophic Signaling.Circulation research · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Phospholipase C-ε defines a PACAP-stimulated pathway for secretion in the chromaffin cell.Journal of neuroendocrinology · 2023Article
- Regulation of cardiac function by cAMP nanodomains.Bioscience reports · 2023Review
- Skeletal muscle derived Musclin protects the heart during pathological overload.Nature communications · 2022Article
- Structure and regulation of phospholipase Cβ and ε at the membrane.Chemistry and physics of lipids · 2021Review
- Review
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Functional and structural characterization of allosteric activation of phospholipase Cε by Rap1A.The Journal of biological chemistry · 2020Article
- Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Calcineurin-AKAP interactions: therapeutic targeting of a pleiotropic enzyme with a little help from its friends.The Journal of physiology · 2020Review
- Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
In cardiac myocytes activation of an exchange factor activated by cAMP (Epac) leads to activation of phospholipase Cε (PLCε)-dependent hydrolysis of phosphatidylinositol 4-phosphate (PI4P) in the Golgi apparatus a process critical for development of cardiac hypertrophy. Here we show that β-adrenergic receptor (βAR) stimulation does not stimulate this pathway in the presence of the broad spectrum phosphodiesterase (PDE) inhibitor IBMX, but selective PDE3 inhibition revealed βAR-dependent PI4P depletion. On the other hand, selective inhibition of PDE2 or PDE9A blocked endothelin-1 (ET-1) and cAMP-dependent PI4P hydrolysis by PLCε. Direct activation of protein kinase A (PKA), protein kinase G (PKG), or the atrial natriuretic factor (ANF) receptor abolished PI4P hydrolysis in response to multiple upstream stimuli. These results reveal distinct pools of cyclic nucleotides that either inhibit PLCε at the Golgi through PKA/PKG, or activate PLCε at the Golgi through Epac. These data together reveal a new mechanism by which ANF and selective PDE inhibitors can protect against cardiac hypertrophy.
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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.