The Myosin Light Chain Kinase Gene Is Not Duplicated in Mouse: Partial Structure and Chromosomal Localization of Mylk

Genomics ◽  
2001 ◽  
Vol 75 (1-3) ◽  
pp. 49-56 ◽  
Author(s):  
Dominique Giorgi ◽  
Concepcion Ferraz ◽  
Marie-Geneviève Mattéi ◽  
Jacques Demaille ◽  
Sylvie Rouquier
Keyword(s):  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Chromosomal Localization ◽  
Partial Structure ◽  
Kinase Gene

scholarly journals Novel Polymorphisms in the Myosin Light Chain Kinase Gene Confer Risk for Acute Lung Injury

2006 ◽  
Vol 34 (4) ◽  
pp. 487-495 ◽  
Author(s):  
Li Gao ◽  
Audrey Grant ◽  
Indrani Halder ◽  
Roy Brower ◽  
Jonathan Sevransky ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Gene

scholarly journals Impact of cardiac myosin light chain kinase gene mutation on development of dilated cardiomyopathy

2019 ◽  
Vol 6 (2) ◽  
pp. 406-415 ◽  
Author(s):  
Akihiko Hodatsu ◽  
Noboru Fujino ◽  
Yuki Uyama ◽  
Osamu Tsukamoto ◽  
Atsuko Imai‐Okazaki ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Gene Mutation ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Cardiac Myosin ◽  
Kinase Gene

scholarly journals Genetic and Epigenetic Regulation of the Non-Muscle Myosin Light Chain Kinase Isoform by Lung Inflammatory Factors and Mechanical Stress

2021 ◽  
Author(s):  
Xiaoguang Sun ◽  
Belinda L Sun ◽  
Saad Sammani ◽  
Tadeo Bermudez ◽  
Steven M. Dudek ◽  
...  
Keyword(s):  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Promoter Activity ◽  
Myosin Light Chain ◽  
Cpg Island ◽  
Cyclic Stretch ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Kinase Gene ◽  
Inflammatory Disorders

Rationale: The myosin light chain kinase gene, MYLK, encodes three proteins via unique promoters, including the non-muscle MLCK isoform (nmMLCK), a cytoskeletal protein centrally involved in regulation of vascular integrity. As MYLK coding SNPs are associated with severe inflammatory disorders (asthma, ARDS), we explored clinical-relevant inflammatory stimuli and promoter SNPs in nmMLCK promoter regulation. Methods: Full-length or serially--deleted MYLK luciferase reporter promoter activities were measured in human lung endothelial cells (EC). SNP-containing nmMYLK DNA fragments were generated and nmMYLK promoter binding by transcription factors detected by protein-DNA electrophoretic mobility shift assay. Promoter demethylation was evaluated by 5-Aza. A preclinical mouse model of LPS-induced acute lung injury (ALI) was utilized for nmMLCK validation. Results: Lung EC levels of nmMLCK were significantly increased in LPS-challenged mice and  LPS, TNFα,  18% cyclic stretch (CS) and 5-Aza each significantly up-regulated EC nmMYLK promoter activities. EC exposure to FG-4592, a prolyl hydroxylase inhibitor that increases hypoxia-inducible factor expression (HIFs), increased nmMYLK promoter activity, confirmed by HIF1α/HIF2α silencing. nmMYLK promoter deletion studies identified distal inhibitory and proximal enhancing promoter regions as well as mechanical stretch-, LPS-, and TNFα-inducible regions. Insertion of ARDS-associated SNPs (rs2700408, rs11714297) significantly increased nmMYLK promoter activity via increased transcription binding (GCM1 and ISX, respectively). Finally, the MYLK rs78755744 SNP (-261G/A), residing within a nmMYLK CpG island, significantly attenuated 5-Aza -induced promoter activity. Conclusion: These findings indicate nmMYLK transcriptional regulation by clinical-relevant inflammatory factors and ARDS-associated nmMYLK promoter variants are consistent with nmMLCK as a therapeutic target in severe inflammatory disorders.

Polymorphisms in the myosin light chain kinase gene that confer risk of severe sepsis are associated with a lower risk of asthma

2007 ◽  
Vol 119 (5) ◽  
pp. 1111-1118 ◽  
Author(s):  
Li Gao ◽  
Audrey V. Grant ◽  
Nicholas Rafaels ◽  
Maria Stockton-Porter ◽  
Tonya Watkins ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Lower Risk ◽  
Myosin Light Chain ◽  
Kinase Gene
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