We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
14-3-3 amplifies and prolongs adrenergic stimulation of HERG K<sup>+</sup> channel activity.
- Authors
Kagan, Anna; Melman, Yonathan F.; Krumerman, Andrew; Mcdonald, Thomas V.
- Abstract
Acute stress provokes lethal cardiac arrhythmias in the hereditary long QT syndrome. Here we provide a novel molecular mechanism linking ß-adrenergic signaling and altered human ether-a-go-go related gene (HERG) channel activity. Stress stimulates ß-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 14-3-3e 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.
- Publication
EMBO Journal, 2002, Vol 21, Issue 8, p1889
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/21.8.1889