The Presence of Lys27 Instead of Asn27 in Human Phospholamban Promotes Sarcoplasmic Reticulum Ca -ATPase Superinhibition and Cardiac Remodeling
نویسندگان
چکیده
Wen Zhao, MD, PhD; Qunying Yuan, MD; Jiang Qian, MD; Jason R. Waggoner, PhD; Anand Pathak, PhD; Guoxiang Chu, MD, PhD; Bryan Mitton, BS; Xiaoyin Sun, MD; Jay Jin, BS; Julian C. Braz, PhD; Harvey S. Hahn, MD; Yehia Marreez, MD; Faisal Syed, MD; Piero Pollesello, PhD; Arto Annila, PhD; Hong-Sheng Wang, PhD; Jo El J. Schultz, PhD; Jeffery D. Molkentin, PhD; Stephen B. Liggett, MD; Gerald W. Dorn II, MD; Evangelia G. Kranias, PhD
منابع مشابه
The presence of Lys27 instead of Asn27 in human phospholamban promotes sarcoplasmic reticulum Ca2+-ATPase superinhibition and cardiac remodeling.
BACKGROUND Phospholamban (PLN) is an inhibitor of the Ca2+ affinity of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2). The amino acid sequence of PLN is highly conserved, and although all species contain asparagine (Asn), human PLN is unique in containing lysine (Lys) at amino acid 27. METHODS AND RESULTS Human PLN was introduced in the null background. Expression of human PLN, at similar l...
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Phospholamban (PLN), the reversible inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), is a key regulator of myocyte Ca(2+) cycling with a significant role in heart failure. We previously showed that the single amino acid difference between human and mouse PLN results in increased inhibition of Ca(2+) cycling and cardiac remodeling and attenuated stress responses in transgen...
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The sarcoplasmic reticulum Ca(2+)-cycling proteins are key regulators of cardiac contractility, and alterations in sarcoplasmic reticulum Ca(2+)-cycling properties have been shown to be causal of familial cardiomyopathies. Through genetic screening of dilated cardiomyopathy patients, we identified a previously uncharacterized deletion of arginine 14 (PLN-R14Del) in the coding region of the phos...
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The Ca-ATPase in the cardiac sarcoplasmic reticulum membrane is regulated by an amphipathic transmembrane protein, phospholamban. We have used time-resolved phosphorescence anisotropy to detect the microsecond rotational dynamics, and thereby the self-association, of the Ca-ATPase as a function of phospholamban phosphorylation and physiologically relevant calcium levels. The phosphorylation of ...
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