Phospholemman: a novel cardiac stress protein.

Citation data:

Clinical and translational science, ISSN: 1752-8062, Vol: 3, Issue: 4, Page: 189-96

Publication Year:
2010
Usage 296
Abstract Views 191
Downloads 95
Full Text Views 10
Captures 19
Readers 18
Exports-Saves 1
Citations 18
Citation Indexes 18
Repository URL:
https://jdc.jefferson.edu/transmedfp/4
PMID:
20718822
DOI:
10.1111/j.1752-8062.2010.00213.x
PMCID:
PMC3013348
Author(s):
Cheung, Joseph Y; Zhang, Xue-Qian; Song, Jianliang; Gao, Erhe; Rabinowitz, Joseph E; Chan, Tung O; Wang, Jufang
Publisher(s):
Wiley-Blackwell
Tags:
Neuroscience; Medicine; Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics; phospholemman; ion transport regulator; protein kinase; Cardiology; Medicine and Health Sciences
review description
Phospholemman (PLM), a member of the FXYD family of regulators of ion transport, is a major sarcolemmal substrate for protein kinases A and C in cardiac and skeletal muscle. In the heart, PLM co-localizes and co-immunoprecipitates with Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and L-type Ca(2+) channel. Functionally, when phosphorylated at serine(68), PLM stimulates Na(+)-K(+)-ATPase but inhibits Na(+)/Ca(2+) exchanger in cardiac myocytes. In heterologous expression systems, PLM modulates the gating of cardiac L-type Ca(2+) channel. Therefore, PLM occupies a key modulatory role in intracellular Na(+) and Ca(2+) homeostasis and is intimately involved in regulation of excitation-contraction (EC) coupling. Genetic ablation of PLM results in a slight increase in baseline cardiac contractility and prolongation of action potential duration. When hearts are subjected to catecholamine stress, PLM minimizes the risks of arrhythmogenesis by reducing Na(+) overload and simultaneously preserves inotropy by inhibiting Na(+)/Ca(2+) exchanger. In heart failure, both expression and phosphorylation state of PLM are altered and may partly account for abnormalities in EC coupling. The unique role of PLM in regulation of Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and potentially L-type Ca(2+) channel in the heart, together with the changes in its expression and phosphorylation in heart failure, make PLM a rational and novel target for development of drugs in our armamentarium against heart failure. Clin Trans Sci 2010; Volume 3: 189-196.