Role of non-kinase activity of myosin light-chain kinase in regulating smooth muscle contraction, a review dedicated to Dr. Setsuro Ebashi.
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.
Nakamura
Akio
A
Department of Molecular and Cellular Pharmacology, Faculty of Medicine, Gunma University, Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan.
Xie
Ce
C
Zhang
Yue
Y
Gao
Ying
Y
Wang
Hong-Hui
HH
Ye
Li-Hong
LH
Kishi
Hiroko
H
Okagaki
Tsuyoshi
T
Yoshiyama
Shinji
S
Hayakawa
Kohichi
K
Ishikawa
Ryoki
R
Kohama
Kazuhiro
K
D000199:Actins / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D004789:Enzyme Activation; D005246:Feedback / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000502:physiology*
D000199:Actins; D009219:Myosin-Light-Chain Kinase