Importin beta plays an essential role in the regulation of the LysRS-Ap4A pathway in immunologically activated mast cells

Abstract

We recently reported that diadenosine tetraphosphate hydrolase (Ap4A hydrolase) plays a critical role in gene expression via regulation of intracellular Ap4A levels. This enzyme serves as a component of our newly described lysyl tRNA synthetase (LysRS)-Ap4A biochemical pathway that is triggered upon immunological challenge. Here we explored the mechanism of this enzyme's translocation into the nucleus and found its immunologically dependent association with importin beta. Silencing of importin beta prevented Ap4A hydrolase nuclear translocation and affected the local concentration of Ap4A, which led to an increase in microphthalmia transcription factor (MITF) transcriptional activity. Furthermore, immunological activation of mast cells resulted in dephosphorylation of Ap4A hydrolase, which changed the hydrolytic activity of the enzyme. © 2011, American Society for Microbiology.