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- W2077261502 startingPage "1889" @default.
- W2077261502 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." @default.
- W2077261502 created "2016-06-24" @default.
- W2077261502 creator A5046774234 @default.
- W2077261502 date "2002-04-15" @default.
- W2077261502 modified "2023-10-18" @default.
- W2077261502 title "14-3-3 amplifies and prolongs adrenergic stimulation of HERG K+ channel activity" @default.
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- W2077261502 doi "https://doi.org/10.1093/emboj/21.8.1889" @default.
- W2077261502 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/125975" @default.
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