Identification of cardiac-specific myosin light chain kinase.
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.
Chan
Jason Y
JY
Department of Physiology and Functional Genomics, University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, FL 32610-0274, USA.
Takeda
Morihiko
M
Briggs
Laura E
LE
Graham
Megan L
ML
Lu
Jonathan T
JT
Horikoshi
Nobuo
N
Weinberg
Ellen O
EO
Aoki
Hiroki
H
Sato
Naruki
N
Chien
Kenneth R
KR
Kasahara
Hideko
H
D000818:Animals; D000831:Animals, Newborn; D024722:Cardiac Myosins / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D006325:Heart Atria / Q000201:enzymology; D006333:Heart Failure / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology; D006352:Heart Ventricles / Q000201:enzymology; D051379:Mice; D008969:Molecular Sequence Data; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000150:complications; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000096:biosynthesis* / Q000235:genetics; D009928:Organ Specificity; D010766:Phosphorylation; D051381:Rats; D012518:Sarcomeres / Q000378:metabolism
D018994:Myosin Light Chains; C107184:myosin light chain 2; D009219:Myosin-Light-Chain Kinase; D024722:Cardiac Myosins