title: Myosin light chain kinase is necessary for tonic airway smooth muscle contraction.
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.
authors.affiliation: Model Animal Research Center of Nanjing University and MOE Key Lab of Model Animal for Disease Study, Nanjing 210061, China.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Zhang
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Peng
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Zhang
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: He
authors.forename: Yan-Ning
authors.initials: YN
authors.lastname: Qiao
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Dong
authors.forename: Yun-Qian
authors.initials: YQ
authors.lastname: Gao
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Cheng-Hai
authors.initials: CH
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Hua-Hao
authors.initials: HH
authors.lastname: Shen
authors.forename: Wen
authors.initials: W
authors.lastname: Ning
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Kamm
authors.forename: James T
authors.initials: JT
authors.lastname: Stull
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Min-Sheng
authors.initials: MS
authors.lastname: Zhu
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001249:Asthma / Q000201:enzymology / Q000235:genetics; D001980:Bronchi / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000201:enzymology*; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D014132:Trachea / Q000201:enzymology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D002147:Calmodulin; D013629:Tamoxifen; D009219:Myosin-Light-Chain Kinase; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium