Myosin light chain kinase is necessary for tonic airway smooth muscle contraction

Wen Cheng Zhang, Ya Jing Peng, Gen Sheng Zhang, Wei Qi He, Yan Ning Qiao, Ying Ying Dong, Yun Qian Gao, Chen Chen, Cheng Hai Zhang, Wen Li, Hua Hao Shen, Wen Ning, Kristine E. Kamm, James T. Stull, Xiang Gao, Min Sheng Zhu

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Abstract

Different interacting signaling modules involving Ca2+/ calmodulin-dependent myosin light chain kinase, Ca2+-independent regulatory light chain phosphorylation, myosin phosphatase inhibition, and actin filament-based proteins are proposed as specific cellular mechanisms involved in the regulation of smooth muscle contraction. However, the relative importance of specific modules is not well defined. By using tamoxifen-activated and smooth muscle-specific knock-out of myosin light chain kinase in mice, we analyzed its role in tonic airway smooth muscle contraction. Knock-out of the kinase in both tracheal and bronchial smooth muscle significantly reduced contraction and myosin phosphorylation responses to K+-depolarization and acetylcholine. Kinase-deficient mice lacked bronchial constrictions in normal and asthmatic airways, whereas the asthmatic inflammation response was not affected. These results indicate that myosin light chain kinase acts as a central participant in the contractile signaling module of tonic smooth muscle. Importantly, contractile airway smooth muscles are necessary for physiological and asthmatic airway resistance.

Original languageEnglish (US)
Pages (from-to)5522-5531
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number8
DOIs
StatePublished - Feb 19 2010

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Zhang, W. C., Peng, Y. J., Zhang, G. S., He, W. Q., Qiao, Y. N., Dong, Y. Y., Gao, Y. Q., Chen, C., Zhang, C. H., Li, W., Shen, H. H., Ning, W., Kamm, K. E., Stull, J. T., Gao, X., & Zhu, M. S. (2010). Myosin light chain kinase is necessary for tonic airway smooth muscle contraction. Journal of Biological Chemistry, 285(8), 5522-5531. https://doi.org/10.1074/jbc.M109.062836