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 language | English (US) |
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Pages (from-to) | 5522-5531 |
Number of pages | 10 |
Journal | Journal of Biological Chemistry |
Volume | 285 |
Issue number | 8 |
DOIs | |
State | Published - Feb 19 2010 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology