O-GlcNAcylation of proteins regulates important cellular processes. A few reports noted that O-GlcNAcylation exhibits cross-talk with tyrosine phosphorylation. With an activity-based microarray analysis of 256 tyrosine kinase peptide substrates, we found that phosphorylation of six peptides by Jak2 inhibits their subsequent O-GlcNAcylation. However, O-GlcNAcylation has no detectable effect on their subsequent phosphorylation. A specific peptide (ZO3_357_371), derived from the ZO-3 protein, was studied in detail. Kinetic results show that the presence of a phosphate at Tyr364 of ZO3_357_371 slows the O-GlcNAcylation of nearby Ser369, while the presence of a GlcNAc at Ser369 has no significant effect on the phosphorylation of this peptide at Tyr364. These findings provide a glimpse into the new paradigm for cellular signaling control by cross-talk.
Keywords: Jak2; O-GlcNAcylation; ZO-3; cross-talk; peptide microarray; tyrosine phosphorylation.
© 2017 Federation of European Biochemical Societies.