ArticleJournal of molecular and cellular cardiology2014
PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling.
Article in Journal of molecular and cellular cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 53 citations in OpenAlex.
- GPCR-selective effects of endocytosis on cellular signaling through the cAMP/PKA cascade.The Journal of biological chemistry · 2026Article
- Single-cell dynamics reveal a stress-induced decision between hypertrophy and apoptosis in neonatal rat cardiomyocytes.Journal of molecular and cellular cardiology plus · 2025Article
- Pulmonary Hypertension-Associated Right Ventricular Cardiomyocyte Remodelling Reduces Treprostinil Function.Cells · 2023Article
- Fluorescent biosensor imaging meets deterministic mathematical modelling: quantitative investigation of signalling compartmentalization.The Journal of physiology · 2023Review
- Status of βReviews in cardiovascular medicine · 2023Review
- Physiological and pathological roles of protein kinase A in the heart.Cardiovascular research · 2022Review
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Differential Activation of P-TEFb Complexes in the Development of Cardiomyocyte Hypertrophy following Activation of Distinct G Protein-Coupled Receptors.Molecular and cellular biology · 2020Article
- 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
- Investigating β-adrenergic-induced cardiac hypertrophy through computational approach: classical and non-classical pathways.The journal of physiological sciences : JPS · 2018Article
- Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in βCell reports · 2018Article
- The p21-activated kinase 1 (Pak1) signalling pathway in cardiac disease: from mechanistic study to therapeutic exploration.British journal of pharmacology · 2018Review
- Using cAMP Sensors to Study Cardiac Nanodomains.Journal of cardiovascular development and disease · 2018Review
- Menin and PRMT5 suppress GLP1 receptor transcript and PKA-mediated phosphorylation of FOXO1 and CREB.American journal of physiology. Endocrinology and metabolism · 2017Article
- Mechanisms of the cyclic nucleotide cross-talk signaling network in cardiac L-type calcium channel regulation.Journal of molecular and cellular cardiology · 2017Article
- AKAP-mediated feedback control of cAMP gradients in developing hippocampal neurons.Nature chemical biology · 2017Article
- Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia.Scientific reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
β-Adrenergic signaling is spatiotemporally heterogeneous in the cardiac myocyte, conferring exquisite control to sympathetic stimulation. Such heterogeneity drives the formation of protein kinase A (PKA) signaling microdomains, which regulate Ca(2+) handling and contractility. Here, we test the hypothesis that the nucleus independently comprises a PKA signaling microdomain regulating myocyte hypertrophy. Spatially-targeted FRET reporters for PKA activity identified slower PKA activation and lower isoproterenol sensitivity in the nucleus (t50=10.6±0.7 min; EC50=89.0 nmol/L) than in the cytosol (t50=3.71±0.25 min; EC50=1.22 nmol/L). These differences were not explained by cAMP or AKAP-based compartmentation. A computational model of cytosolic and nuclear PKA activity was developed and predicted that differences in nuclear PKA dynamics and magnitude are regulated by slow PKA catalytic subunit diffusion, while differences in isoproterenol sensitivity are regulated by nuclear expression of protein kinase inhibitor (PKI). These were validated by FRET and immunofluorescence. The model also predicted differential phosphorylation of PKA substrates regulating cell contractility and hypertrophy. Ca(2+) and cell hypertrophy measurements validated these predictions and identified higher isoproterenol sensitivity for contractile enhancements (EC50=1.84 nmol/L) over cell hypertrophy (EC50=85.9 nmol/L). Over-expression of spatially targeted PKA catalytic subunit to the cytosol or nucleus enhanced contractile and hypertrophic responses, respectively. We conclude that restricted PKA catalytic subunit diffusion is an important PKA compartmentation mechanism and the nucleus comprises a novel PKA signaling microdomain, insulating hypertrophic from contractile β-adrenergic signaling responses.
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.