Role of non-kinase activity of myosin light-chain kinase in regulating smooth muscle contraction, a review dedicated to Dr. Setsuro Ebashi

• Published in: Biochemical and biophysical research communications Vol. 369; no. 1; pp. 135 - 143
• Main Authors: Nakamura, Akio, Xie, Ce, Zhang, Yue, Gao, Ying, Wang, Hong-Hui, Ye, Li-Hong, Kishi, Hiroko, Okagaki, Tsuyoshi, Yoshiyama, Shinji, Hayakawa, Kohichi, Ishikawa, Ryoki, Kohama, Kazuhiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.04.2008
• Subjects: Actin-binding activity; Actins - physiology; Actin–myosin interaction; Animals; Calcium regulation; Calcium Signaling - physiology; Calmodulin; Contraction of smooth muscle; Domain structure of myosin light-chain kinase; Enzyme Activation; Feedback - physiology; Humans; Kinase activity; Models, Biological; Muscle Contraction - physiology; Muscle, Smooth - physiology; Myosin light-chain kinase; Myosin-binding activity; Myosin-Light-Chain Kinase - physiology; Non-kinase activity; Kinase activity; Actin-binding activity; Actin–myosin interaction; Myosin-binding activity; Non-kinase activity; Domain structure of myosin light-chain kinase; Contraction of smooth muscle; Myosin light-chain kinase; Calmodulin; Calcium regulation
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.11.096

Myosin light-chain kinase (MLCK) of smooth muscle consists of an actin-binding domain at the N-terminal, the catalytic domain in the central portion, and the myosin-binding domain at the C-terminal. The kinase activity is mediated by the catalytic domain that phosphorylates the myosin light-chain of 20kDa (MLC20), activating smooth muscle myosin to interact with actin. Although the regulatory role of the kinase activity is well established, the role of non-kinase activity derived from actin-binding and myosin-binding domains remains unknown. This review is dedicated to Dr. Setsuro Ebashi, who devoted himself to elucidating the non-kinase activity of MLCK after establishing calcium regulation through troponin in skeletal and cardiac muscles. He proposed that the actin–myosin interaction of smooth muscle could be activated by the non-kinase activity of MLCK, a mechanism that is quite independent of MLC20 phosphorylation. The authors will extend his proposal for the role of non-kinase activity. In this review, we express MLCK and its fragments as recombinant proteins to examine their effects on the actin–myosin interaction in vitro. We also down-regulate MLCK in the cultured smooth muscle cells, and propose that MLC20 phosphorylation is not obligatory for the smooth muscle to contract.