共 53 条
14-3-3 amplifies and prolongs adrenergic stimulation of HERG K+ channel activity
被引:120
作者:

Kagan, A
论文数: 0 引用数: 0
h-index: 0
机构: Yeshiva Univ Albert Einstein Coll Med, Dept Med, Sect Mol Cardiol, Bronx, NY 10461 USA

Melman, YF
论文数: 0 引用数: 0
h-index: 0
机构: Yeshiva Univ Albert Einstein Coll Med, Dept Med, Sect Mol Cardiol, Bronx, NY 10461 USA

Krumerman, A
论文数: 0 引用数: 0
h-index: 0
机构: Yeshiva Univ Albert Einstein Coll Med, Dept Med, Sect Mol Cardiol, Bronx, NY 10461 USA

McDonald, TV
论文数: 0 引用数: 0
h-index: 0
机构: Yeshiva Univ Albert Einstein Coll Med, Dept Med, Sect Mol Cardiol, Bronx, NY 10461 USA
机构:
[1] Yeshiva Univ Albert Einstein Coll Med, Dept Med, Sect Mol Cardiol, Bronx, NY 10461 USA
[2] Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Sect Mol Cardiol, Bronx, NY 10461 USA
关键词:
14-3-3;
cAMP;
HERG;
PKA;
potassium channel;
D O I:
10.1093/emboj/21.8.1889
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
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.
引用
收藏
页码:1889 / 1898
页数:10
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