Study of cross talk between phosphatases and OGA on a ZO-3-derived peptide

Abstract

O-GlcNAcylation, like phosphorylation, is a dynamic and rapid posttranslational modification which regulates many cellular processes. Phosphorylation on tyrosine and O-GlcNAcylation on nearby serine or threonine residues may modulate each other. Indeed, by using a microarray with a peptide model system based on the ZO-3 protein, extensive cross talk between O-GlcNAcylation by OGT and phosphorylation by kinases was observed. However, studying the effects of kinases and OGT without the reverse processes catalyzed by phosphatases and O-GlcNAcase (OGA) does not provide a complete picture of the cross talk. The study of the missing part showed that nearby phosphorylation affects the de-O-GlcNAcylation by OGA, but not to the same extent as it affects the O-GlcNAcylation by OGT. Both the phosphorylation and de-phosphorylation processes were only slightly affected by the presence of an O-GlcNAc residue on a nearby serine.