doi: 10.1161/CIRCRESAHA.108.173005
© 2008 American Heart Association, Inc.
Editorials |
Cardiac Myosin Light Chain Kinase
A New Player in the Regulation of Myosin Light Chain in the Heart
From the Cardiovascular Research Institute (Y.I.), Departments of Cell Biology & Molecular Medicine and Department of Medicine (Cardiology), New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark; and Cardiovascular Research Institute (Y.I., R.K.), Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Correspondence to Yoshihiro Ishikawa, MD, PhD, Cardiovascular Research Institute, Departments of Medicine (Cardiology) and Cell Biology & Molecular Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 S Orange Ave, Newark, NJ 07103. E-mail ishikayo@umdnj.edu
See related article, pages 571–580
Key Words: myosin light chain kinase • cardiac subtype • cardiac function • regulatory myosin light chain
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Muscle myosin, which is the highly conserved molecular motor, contains 1 pair of myosin heavy chains (MHCs) and 2 pairs of myosin light chains (MLCs), the latter of which are referred to as essential and regulatory light chains.1,2 It is well known that muscle myosin is regulated through the phosphorylation of regulatory MLC (MLC2). In smooth muscles, for example, phosphorylation of MLC2 by MLC kinase (MLCK) activates the actin-activated myosin ATPase, leading to muscular contraction. In skeletal muscles, in contrast, the actin-myosin interaction is regulated by the troponin–tropomyosin complex, and MLC2 only modestly regulates rate and magnitude of contractile force generation. Thus, the role of MLC2 and the significance of its phosphorylation by MLCK may differ among tissues.
It is well expected that MLC2 plays a major role in regulating cardiac function as well. Such importance of MLC2 has been suggested in human genetic studies. Mutations in MLC2 have been shown in numerous analyses to be well correlated with the occurrence of certain forms of hypertrophic cardiomyopathy.3 Such MLC2 is phosphorylated by MLCK, and, therefore, the expression and activity of this kinase must play an important role in the heart as well. In accordance with this concept, MLCK phosphorylation in the heart can also regulate muscle contractility by increasing the Ca2+ sensitivity of force and accelerating the stretch activation response,4 and the state of MLCK phosphorylation through the thickness of the ventricular walls indeed is not uniform, but a spatial gradient exists, and this gradient is a major determinant of
Related Article:
Circ. Res. 2008 102: 571-580.