Two myosin light chain (MLC) kinase (MLCK) proteins, smooth muscle (encoded by mylk1 gene) and skeletal (encoded by mylk2 gene) MLCK, have been shown to be expressed in mammals. Even though phosphorylation of its putative substrate, MLC2, is recognized as a key regulator of cardiac contraction, a MLCK that is preferentially expressed in cardiac muscle has not yet been identified. In this study, we characterized a new kinase encoded by a gene homologous to mylk1 and -2, named cardiac MLCK, which is specifically expressed in the heart in both atrium and ventricle. In fact, expression of cardiac MLCK is highly regulated by the cardiac homeobox protein Nkx2-5 in neonatal cardiomyocytes. The overall structure of cardiac MLCK protein is conserved with skeletal and smooth muscle MLCK; however, the amino terminus is quite unique, without significant homology to other known proteins, and its catalytic activity does not appear to be regulated by Ca(2+)/calmodulin in vitro. Cardiac MLCK is phosphorylated and the level of phosphorylation is increased by phenylephrine stimulation accompanied by increased level of MLC2v phosphorylation. Both overexpression and knockdown of cardiac MLCK in cultured cardiomyocytes revealed that cardiac MLCK is likely a new regulator of MLC2 phosphorylation, sarcomere organization, and cardiomyocyte contraction.
Identification of cardiac-specific myosin light chain kinase. Publishing Authors By Initials
Identification of cardiac-specific myosin light chain kinase. Journal Published:
PUBLICATION TYPE: Research Support, Non-U.S. Gov
Journal: Circulation research
VOLUME: 102
Page Numbers: 571-80
Journal Abbreviation: Circ. Res.
ISSN: 1524-4571
DAY: 17
MONTH: 01
YEAR: 2008
Identification of cardiac-specific myosin light chain kinase. Information
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LANGUAGE: eng
NlmUniqueID: 47103
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Grant and Affiliation Information for Identification of cardiac-specific myosin light chain kinase.
AFFILIATION: Department of Physiology and Functional Genomics, University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, FL 32610-0274, USA.
Country: United States
AGENCY: United States NHLBI
GRANT: HL081577
ACRONYM: HL
MEDLINETA: Circ Res
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