Dyrk2 involved in regulating LPS-induced neuronal apoptosis

Abstract The activation of relevant signaling pathways plays a very important role in LPS-induced neuronal damage. Dual-specificity tyrosine-phosphorylation-regulated kinase 2(Dyrk2), as a phosphokinase that can directly or indirectly phosphorylate signal molecules, was recently reported to down-regulate Type I Interferon(TIF) by promoting ser527 phosphorylation of TBK1. To further investigate the role of Dyrk2 in neuroinflammation, we for the first time focused on its function in LPS-induced neuronal damage. We found LPS stimulation increased the expression of Dyrk2 in the nucleus and cytoplasm of neurons. In addition, overexpression of Dyrk2 not only reduced the level of TNF-α induction, but also obviously inhibited LPS-induced neuronal apoptosis. We further found that Dyrk2 promoted the induction of phospho-Akt, phospho-p65 and phospho-p38MAPK (p38 mitogen-activated protein kinase), but immunoprecipitation showed Dyrk2 interacted with and Akt, p38MAPK and IκBα (IkappaB-alpha), except NF-κB subunit p65. These findings suggest Dyrk2 can inhibit LPS-induced neuronal apoptosis and plays key roles in LPS-indcued signaling pathways by its phosphokinase function. These data provide a novel viewpoint that Dyrks family may have an important role in neuroinflammation, and provide a potential molecular target for improving neuronal apoptosis.