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.
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.
Akio
A
Nakamura
Ce
C
Xie
Yue
Y
Zhang
Ying
Y
Gao
Hong-Hui
HH
Wang
Li-Hong
LH
Ye
Hiroko
H
Kishi
Tsuyoshi
T
Okagaki
Shinji
S
Yoshiyama
Kohichi
K
Hayakawa
Ryoki
R
Ishikawa
Kazuhiro
K
Kohama
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