o-GlcNAc transferase is activated by CaMKIV-dependent phosphorylation under potassium chloride-induced depolarization in NG-108-15 cells.
Post-translational modification of cellular proteins by beta-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.
Song
Minseok
M
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Kyung-Buk 790-784, Republic of Korea.
Kim
Hyeon-Soo
HS
Park
Ji-Man
JM
Kim
Sun-Hee
SH
Kim
In-Hoo
IH
Ryu
Sung Ho
SH
Suh
Pann-Ghill
PG
D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D018808:Transcription Factor AP-1; D011189:Potassium Chloride; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D002118:Calcium