Myosin light chain kinase ( MYLK) coding polymorphisms modulate human lung endothelial cell barrier responses via altered tyrosine phosphorylation, spatial localization, and lamellipodial protrusions

Pulmonary Circulation
Ting WangJoe G N Garcia

Abstract

Sphingosine 1-phosphate (S1P) is a potent bioactive endogenous lipid that signals a rearrangement of the actin cytoskeleton via the regulation of non-muscle myosin light chain kinase isoform (nmMLCK). S1P induces critical nmMLCK Y464 and Y471 phosphorylation resulting in translocation of nmMLCK to the periphery where spatially-directed increases in myosin light chain (MLC) phosphorylation and tension result in lamellipodia protrusion, increased cell-cell adhesion, and enhanced vascular barrier integrity. MYLK, the gene encoding nmMLCK, is a known candidate gene in lung inflammatory diseases, with coding genetic variants (Pro21His, Ser147Pro, Val261Ala) that confer risk for inflammatory lung injury and influence disease severity. The functional mechanisms by which these MYLK coding single nucleotide polymorphisms (SNPs) affect biologic processes to increase disease risk and severity remain elusive. In the current study, we utilized quantifiable cell immunofluorescence assays to determine the influence of MYLK coding SNPs on S1P-mediated nmMLCK phosphorylation and translocation to the human lung endothelial cell (EC) periphery . These disease-associated MYLK variants result in reduced levels of S1P-induced Y464 phosphorylation, a...Continue Reading

References

Jan 5, 1995·The New England Journal of Medicine·M H Kollef, D P Schuster
Aug 1, 1996·Archives of Biochemistry and Biophysics·H W DavisJ G Garcia
Apr 13, 1999·Genomics·V Lazar, J G Garcia
Sep 25, 2001·Journal of Applied Physiology·S M Dudek, J G Garcia
Jun 28, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Feng LiuJoe G N Garcia
Nov 1, 2002·Biochemical and Biophysical Research Communications·Steven M DudekJoe G N Garcia
Mar 13, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Irina PetracheJoe G N Garcia
Jan 10, 2006·American Journal of Respiratory Cell and Molecular Biology·Li GaoJoe G N Garcia
Mar 26, 2013·Nanomedicine : Nanotechnology, Biology, and Medicine·Fernando Terán ArceRatnesh Lal
Sep 17, 2013·American Journal of Respiratory and Critical Care Medicine·Joe G N Garcia, Jacob I Sznajder
Jan 17, 2014·American Journal of Respiratory Cell and Molecular Biology·Ting WangJoe G N Garcia
Jun 3, 2014·American Journal of Respiratory and Critical Care Medicine·Franziska J RosserJuan C Celedón
Oct 2, 2014·European Journal of Human Genetics : EJHG·Ting WangJoe Gn Garcia
May 31, 2015·The Journal of Allergy and Clinical Immunology·Marialbert Acosta-HerreraCarlos Flores
Jul 31, 2016·Biochemical and Biophysical Research Communications·P ViswanathanS M Dudek
Aug 17, 2016·American Journal of Respiratory Cell and Molecular Biology·Joseph B MascarenhasJoe G N Garcia

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Citations

Oct 28, 2017·American Journal of Respiratory Cell and Molecular Biology·Joseph B MascarenhasJoe G N Garcia
Jul 18, 2018·The Journal of Physiology·Szandor SimmonsWolfgang M Kuebler
Jun 22, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Stephanie E WallaceDianna M Milewicz
Apr 25, 2019·Antioxidants & Redox Signaling·Heather LynnJoe G N Garcia
Oct 29, 2020·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Dane W SorensenWilliam J Pearce

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Methods Mentioned

BETA
confocal microscopy
transfection
atomic force microscopy
AFM
nuclear magnetic resonance
NMR

Software Mentioned

ImageJ
Multiple Kymograph Plugin
Leica LAS AF

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