This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 102/5/571    most recent CIRCRESAHA.107.161687v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Google Scholar Articles by Chan, J. Y. Articles by Kasahara, H. PubMed PubMed Citation Articles by Chan, J. Y. Articles by Kasahara, H. Related Collections Contractile function Gene expression Heart failure - basic studies Physiological and pathological control of gene expression Related Article

(Circulation Research. 2008;102:571.)
© 2008 American Heart Association, Inc.

Cellular Biology

Identification of Cardiac-Specific Myosin Light Chain Kinase

Jason Y. Chan^*, Morihiko Takeda^*, Laura E. Briggs^*, Megan L. Graham, Jonathan T. Lu, Nobuo Horikoshi, Ellen O. Weinberg, Hiroki Aoki, Naruki Sato, Kenneth R. Chien, Hideko Kasahara

From the Department of Physiology and Functional Genomics (J.Y.C., M.T., L.E.B., M.L.G., H.K.), University of Florida College of Medicine, Gainesville, Fla; Cardiology Division (J.T.L.), University of California, San Francisco; Department of Radiation Oncology (N.H.), Washington University School of Medicine, St Louis, Mo; Cardiovascular Research (E.O.W.), Boston University Medical Center, Boston, Mass; Department of Molecular Cardiovascular Biology (H.A.), Yamaguchi University School of Medicine, Ube, Japan; Department of Biology (N.S.), Faculty of Science, Chiba University, Chiba, Japan; and Cardiovascular Research Center (K.R.C.), Massachusetts General Hospital, Boston.

Correspondence to Hideko Kasahara, MD, PhD, Department of Physiology and Functional Genomics, University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, FL 32610-0274. E-mail hkasahar{at}phys.med.ufl.edu

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 Ca²⁺/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.

Key Words: kinase • transcription • contraction

Related Article:

Cardiac Myosin Light Chain Kinase: A New Player in the Regulation of Myosin Light Chain in the Heart

Yoshihiro Ishikawa and Reiko Kurotani
Circ. Res. 2008 102: 516-518. [Full Text] [PDF]

This article has been cited by other articles:

				J. Huang, J. M. Shelton, J. A. Richardson, K. E. Kamm, and J. T. Stull Myosin Regulatory Light Chain Phosphorylation Attenuates Cardiac Hypertrophy J. Biol. Chem., July 11, 2008; 283(28): 19748 - 19756. [Abstract] [Full Text] [PDF]

				Y. Ishikawa and R. Kurotani Cardiac Myosin Light Chain Kinase: A New Player in the Regulation of Myosin Light Chain in the Heart Circ. Res., March 14, 2008; 102(5): 516 - 518. [Full Text] [PDF]