Abstract
Post-translational modification of cellular proteins by β- o-linked N-acetylglucosamine ( o-GlcNAc) moieties plays a significant role in signal transduction by modulating protein stability, protein–protein interactions, transactivation processes, and the enzyme activities of target proteins. Though various classes of proteins are known to be regulated by o-GlcNAc modification ( o-GlcNAcylation), the mechanism that regulates o-linked GlcNAc transferase (OGT) activity remains unknown. Here, we report that potassium chloride-induced depolarization provokes the activation of OGT and subsequent o-GlcNAcylation of proteins in neuroblastoma NG-108-15 cells. Moreover, such an induction of protein o-GlcNAcylation was abolished by treating cells with either a voltage-gated calcium channel inhibitor or a calcium/calmodulin-dependent protein kinase (CaMK) inhibitor. In addition, CaMKIV was found to specifically phosphorylate and activate OGT in vivo and in vitro, which implies that CaMKIV is required for depolarization-induced activation of OGT. Furthermore, we found that OGT is involved in depolarization-induced and CaMKIV-dependent activation of activator protein-1 (AP-1) and subsequent tissue inhibitor of metalloproteinase-1 (Timp-1) gene expression. Taken together, our findings suggest that CaMKIV activated OGT, and OGT has an essential role on the process of CaMKIV-dependent AP-1 activation under depolarization in neuronal cells.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.