ArticleThe EMBO journal2002
14-3-3 amplifies and prolongs adrenergic stimulation of HERG K+ channel activity.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 138 citations in OpenAlex.
- 14-3-3 proteins: Regulators of cardiac excitation-contraction coupling and stress responses.The Journal of physiology · 2026Review
- Identification of 14-3-3 Proteins as Binding Partners of TRP Channels.Journal of chemical information and modeling · 2026Article
- 14-3-3 promotes sarcolemmal expression of cardiac CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The proteostasis interactomes of trafficking-deficient variants of the voltage-gated potassium channel KThe Journal of biological chemistry · 2024Article
- 14-3-3ε: a protein with complex physiology function but promising therapeutic potential in cancer.Cell communication and signaling : CCS · 2024Review
- 14-3-3 protein regulation of excitation-contraction coupling.Pflugers Archiv : European journal of physiology · 2022Review
- Cnksr2 Loss in Mice Leads to Increased Neural Activity and Behavioral Phenotypes of Epilepsy-Aphasia Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- Proteomic Analysis of Exosomes during Cardiogenic Differentiation of Human Pluripotent Stem Cells.Cells · 2021Article
- Identification of Aberrantly Expressed lncRNAs Involved in Orthodontic Force Using a Subpathway Strategy.Computational and mathematical methods in medicine · 2019Article
- Inherited Cardiomyopathies and the Role of Mutations in Non-coding Regions of the Genome.Frontiers in cardiovascular medicine · 2018Review
- Kv4.3 Modulates the Distribution of hERG.Scientific reports · 2017Article
- Drug-Mediated Shortening of Action Potentials in LQTS2 Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Stem cells and development · 2017Article
- Kir2.1-Nav1.5 Channel Complexes Are Differently Regulated than Kir2.1 and Nav1.5 Channels Alone.Frontiers in physiology · 2017Article
- Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease.The Journal of physiology · 2016Review
- A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1.Journal of cell science · 2016Article
- Molecular Mechanisms of Sympathetic Remodeling and Arrhythmias.Circulation. Arrhythmia and electrophysiology · 2016Review
- The nervous heart.Progress in biophysics and molecular biology · 2016Review
- Downregulation of urea transporter UT-A1 activity by 14-3-3 protein.American journal of physiology. Renal physiology · 2015Article
- Ion channel macromolecular complexes in cardiomyocytes: roles in sudden cardiac death.Circulation research · 2015Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Acute stress provokes lethal cardiac arrhythmias in the hereditary long QT syndrome. Here we provide a novel molecular mechanism linking beta-adrenergic signaling and altered human ether-a-go-go related gene (HERG) channel activity. Stress stimulates beta-adrenergic receptors, leading to cAMP elevations that can regulate HERG K+ channels both directly and via phosphorylation by cAMP-dependent protein kinase (PKA). We show that HERG associates with 14-3-3epsilon to potentiate cAMP/PKA effects upon HERG. The binding of 14-3-3 occurs simultaneously at the N- and C-termini of the HERG channel. 14-3-3 accelerates and enhances HERG activation, an effect that requires PKA phosphorylation of HERG and dimerization of 14-3-3. The interaction also stabilizes the lifetime of the PKA-phosphorylated state of the channel by shielding the phosphates from cellular phosphatases. The net result is a prolongation of the effect of adrenergic stimulation upon HERG activity. Thus, 14-3-3 interactions with HERG may provide a unique mechanism for plasticity in the control of membrane excitability and cardiac rhythm.
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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.