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

Research output: Contribution to journalArticle

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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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Myosin-Light-Chain Kinase
Muscle Contraction
Smooth Muscle
Muscle
Phosphorylation
Phosphotransferases
Myosin-Light-Chain Phosphatase
Airway Resistance
Bronchoconstriction
Depolarization
Tamoxifen
Calmodulin
Myosins
Actin Cytoskeleton
Acetylcholine
Actins
Inflammation
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Zhang, W. C., Peng, Y. J., Zhang, G. S., He, W. Q., Qiao, Y. N., Dong, Y. Y., ... 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

Myosin light chain kinase is necessary for tonic airway smooth muscle contraction. / Zhang, Wen Cheng; Peng, Ya Jing; Zhang, Gen Sheng; He, Wei Qi; Qiao, Yan Ning; Dong, Ying Ying; Gao, Yun Qian; Chen, Chen; Zhang, Cheng Hai; Li, Wen; Shen, Hua Hao; Ning, Wen; Kamm, Kristine E.; Stull, James T.; Gao, Xiang; Zhu, Min Sheng.

In: Journal of Biological Chemistry, Vol. 285, No. 8, 19.02.2010, p. 5522-5531.

Research output: Contribution to journalArticle

Zhang, WC, Peng, YJ, Zhang, GS, He, WQ, Qiao, YN, Dong, YY, Gao, YQ, Chen, C, Zhang, CH, Li, W, Shen, HH, Ning, W, Kamm, KE, Stull, JT, Gao, X & Zhu, MS 2010, 'Myosin light chain kinase is necessary for tonic airway smooth muscle contraction', Journal of Biological Chemistry, vol. 285, no. 8, pp. 5522-5531. https://doi.org/10.1074/jbc.M109.062836
Zhang, Wen Cheng ; Peng, Ya Jing ; Zhang, Gen Sheng ; He, Wei Qi ; Qiao, Yan Ning ; Dong, Ying Ying ; Gao, Yun Qian ; Chen, Chen ; Zhang, Cheng Hai ; Li, Wen ; Shen, Hua Hao ; Ning, Wen ; Kamm, Kristine E. ; Stull, James T. ; Gao, Xiang ; Zhu, Min Sheng. / Myosin light chain kinase is necessary for tonic airway smooth muscle contraction. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 8. pp. 5522-5531.
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