Mechanical Stress and Single Nucleotide Variants Regulate Alternative Splicing of the MYLK Gene.

ABSTRACT: The nonmuscle (nm) myosin light-chain kinase isoform (MLCK), encoded by the MYLK gene, is a vital participant in regulating vascular barrier responses to mechanical and inflammatory stimuli. We determined that MYLK is alternatively spliced, yielding functionally distinct nmMLCK splice variants including nmMLCK2, a splice variant highly expressed in vascular endothelial cells (EC) and associated with reduced EC barrier integrity. We demonstrated previously that the nmMLCK2 variant lacks exon 11, which encodes a key regulatory region containing two differentially phosphorylated tyrosine residues (Y⁴⁶⁴ and Y⁴⁷¹) that influence vascular barrier function during inflammation. In this study, we used minigene constructs and RT-PCR to interrogate biophysical factors (mechanica

SUBMITTER: Mascarenhas JB 

PROVIDER: S-EPMC5248959 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature