Inactivation of phosphatidylinositol 4-kinase IIIalpha (PI4KA) by GSK-A1 inhibitor in HEK293 cells

Phosphatidylinositol 4-kinases (PI4Ks) are lipid kinase enzymes that play important roles in cellular signaling, membrane trafficking, viral replication and lipid metabolism. They catalyze the phosphorylation of phosphatidylinositol (PI) to produce phosphatidylinositol 4-phosphate (PI4P) at various organelle membranes. Among the four isoforms of PI4Ks, PI4KA is localized at the plasma membrane where it generates the lipid, PI4P. GSK-A1 is a well-characterized and specific inhibitor of PI4KA. In this study, we investigated transcriptional changes that occur following prolonged (24 h) treatment with GSK-A1. This RNA-seq analysis revealed significant changes in the mRNA levels of a distinct set of proteins, including transcription factors and small GTP-binding proteins. These changes were analyzed in the context of overall lipid level alterations induced by GSK-A1 treatment, as determined by lipidomic analyses. Overall design: RNA-seq profiling of HEK293 cells treated with dimethyl sulfoxide (DMSO) or GSK-A1 for 24 hours.