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Myosin light chain kinase is necessary for tonic airway smooth muscle contraction.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2010 Feb 19; Vol. 285 (8), pp. 5522-31. Date of Electronic Publication: 2009 Dec 14. - Publication Year :
- 2010
-
Abstract
- Different interacting signaling modules involving Ca(2+)/calmodulin-dependent myosin light chain kinase, Ca(2+)-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.
- Subjects :
- Acetylcholine metabolism
Airway Resistance drug effects
Airway Resistance physiology
Animals
Antineoplastic Agents, Hormonal pharmacology
Asthma enzymology
Asthma genetics
Calcium metabolism
Calmodulin metabolism
Female
Male
Mice
Mice, Transgenic
Muscle Contraction drug effects
Muscle Tonus drug effects
Myosin-Light-Chain Kinase genetics
Phosphorylation drug effects
Phosphorylation physiology
Potassium metabolism
Signal Transduction drug effects
Signal Transduction physiology
Tamoxifen pharmacology
Bronchi enzymology
Muscle Contraction physiology
Muscle Tonus physiology
Muscle, Smooth enzymology
Myosin-Light-Chain Kinase metabolism
Trachea enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 285
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20018858
- Full Text :
- https://doi.org/10.1074/jbc.M109.062836