scholarly journals Nonmuscle Myosin Light Chain Kinase Activity Modulates Radiation-Induced Lung Injury

2016 ◽  
Vol 6 (2) ◽  
pp. 234-239 ◽  
Author(s):  
Ting Wang ◽  
Biji Mathew ◽  
Xiaomin Wu ◽  
Yuka Shimizu ◽  
Alicia N. Rizzo ◽  
...  
Keyword(s):  
Lung Injury ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Activity ◽  
Nonmuscle Myosin ◽  
Radiation Induced

scholarly journals Abl Tyrosine Kinase Phosphorylates Nonmuscle Myosin Light Chain Kinase to Regulate Endothelial Barrier Function

2010 ◽  
Vol 21 (22) ◽  
pp. 4042-4056 ◽  
Author(s):  
Steven M. Dudek ◽  
Eddie T. Chiang ◽  
Sara M. Camp ◽  
Yurong Guo ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Activity ◽  
Actin Binding ◽  
Nonmuscle Myosin ◽  
Cortical Actin ◽  
Abl Kinase ◽  
Barrier Regulation

Nonmuscle myosin light chain kinase (nmMLCK), a multi-functional cytoskeletal protein critical to vascular homeostasis, is highly regulated by tyrosine phosphorylation. We identified multiple novel c-Abl–mediated nmMLCK phosphorylation sites by mass spectroscopy analysis (including Y231, Y464, Y556, Y846) and examined their influence on nmMLCK function and human lung endothelial cell (EC) barrier regulation. Tyrosine phosphorylation of nmMLCK increased kinase activity, reversed nmMLCK-mediated inhibition of Arp2/3-mediated actin polymerization, and enhanced binding to the critical actin-binding phosphotyrosine protein, cortactin. EC challenge with sphingosine 1-phosphate (S1P), a potent barrier-enhancing agonist, resulted in c-Abl and phosphorylated nmMLCK recruitment into caveolin-enriched microdomains, rapid increases in Abl kinase activity, and spatial targeting of c-Abl to barrier-promoting cortical actin structures. Conversely, reduced c-Abl expression in EC (siRNA) markedly attenuated S1P-mediated cortical actin formation, reduced the EC modulus of elasticity (assessed by atomic force microscopy), reduced nmMLCK and cortactin tyrosine phosphorylation, and attenuated S1P-mediated barrier enhancement. These studies indicate an essential role for Abl kinase in vascular barrier regulation via posttranslational modification of nmMLCK and strongly support c-Abl-cortactin-nmMLCK interaction as a novel determinant of cortical actin-based cytoskeletal rearrangement critical to S1P-mediated EC barrier enhancement.

scholarly journals MicroRNA Regulation of Nonmuscle Myosin Light Chain Kinase Expression in Human Lung Endothelium

2013 ◽  
Vol 49 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Djanybek M. Adyshev ◽  
Nurgul Moldobaeva ◽  
Brandon Mapes ◽  
Venkate Elangovan ◽  
Joe G. N. Garcia
Keyword(s):  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Human Lung ◽  
Nonmuscle Myosin ◽  
Microrna Regulation ◽  
Lung Endothelium ◽  
Kinase Expression

scholarly journals Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating β2 integrins

2008 ◽  
Vol 9 (8) ◽  
pp. 880-886 ◽  
Author(s):  
Jingsong Xu ◽  
Xiao-Pei Gao ◽  
Ramaswamy Ramchandran ◽  
You-Yang Zhao ◽  
Stephen M Vogel ◽  
...  
Keyword(s):  
Light Chain ◽  
Lung Inflammation ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Nonmuscle Myosin ◽  
Β2 Integrins

Regulation of Myosin Light Chain Kinase Activity in Smooth Muscle

1995 ◽  
pp. 139-158 ◽  
Author(s):  
Kristine E. Kamm ◽  
Katherine Luby-Phelps ◽  
Malu G. Tansey ◽  
Patricia J. Gallagher ◽  
James T. Stull
Keyword(s):  
Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Activity

Role of calmodulin and myosin light-chain kinase in lung ischemia-reperfusion injury

1996 ◽  
Vol 271 (1) ◽  
pp. L121-L125 ◽  
Author(s):  
P. L. Khimenko ◽  
T. M. Moore ◽  
P. S. Wilson ◽  
A. E. Taylor
Keyword(s):  
Endothelial Cell ◽  
Lung Injury ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Ischemia Reperfusion ◽  
Calcium Ionophore ◽  
Microvascular Permeability ◽  
Microvascular Damage ◽  
Pkc Inhibitor

It is generally accepted that microvascular permeability is controlled by intercellular endothelial cell gap size. This process is controlled in endothelial cell monolayers and peripheral blood vessels by calmodulin (CaM)-dependent myosin light-chain kinase (MLCK), which phosphorylates MLC20 with subsequent actin-myosin interaction. In the present study both CaM and MLCK blockers were studied during ischemia-reperfusion (I/R)-induced injury in isolated buffer-perfused rat lungs. The effects of a calcium ionophore (CaI) were tested in isolated intact rat lungs to compare the effects of increasing intracellular Ca2+ to I/R-induced damage. Because protein kinase C (PKC) could also be a mediator of I/R injury, a PKC inhibitor was studied in lungs subjected to either I/R or CaI. In lungs subjected to I/R alone, a fivefold increase in microvascular permeability occurred after 30 min of reperfusion (P < 0.001), and a tenfold increase was present after an additional 60 min of reperfusion (P < 0.01). Pretreatment of the I/R lungs with a CaM inhibitor (trifluoperazine, 100 microM) or with a MLCK inhibitor (ML-7,500 nM) blocked the microvascular damage at both 30 and 90 min of reperfusion. When the CaM inhibitor was introduced into the venous reservoir after 46 min of reperfusion, after the microvascular damage was present, no further increase in microvascular permeability occurred. Pretreatment of the lungs with a PKC inhibitor (staurosporine, 100 nM) did not alter the magnitude of the increased microvascular permeability produced by I/R or the time course of the damage. The calcium ionophore A23187 (7.5 microM) caused increases in Kfc values similar to those produced by I/R. Pretreatment of A23187-treated lungs with a CaM inhibitor produced no protective effect on the microvascular injury at 30 min after administration. Pretreatment of the CaI-challenged lungs with staurosporine significantly increased the microvascular barrier injury at 30 min compared with that occurring with I/R. When a beta-adrenergic receptor agonist (isoproterenol, 10 microM) was introduced to the lung after CaI-induced damage had occurred, no further increase in microvascular permeability was observed, and a trend toward reversal of injury occurred. We conclude from these studies that CaM/MLCK/MLC20 system is involved in our model of I/R-induced rat lung injury but is not involved in lung injury associated with Ca2+ entering the cell.

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