Elucidating crosstalk mechanisms between phosphorylation and O-GlcNAcylation

• DOI: 10.1073/pnas.1620529114
• Publication Date: 2017-08-15T00:50:24Z
• Authors: Aneika C. Leney; Dris El Atmioui; Wei Wu; Huib Ovaa; Albert J. R. Heck
• Keywords: Crosstalk; Proteome; Transferase

Significance Nearly all proteins are posttranslationally modified, a phenomenon known to alter protein function. Recently, multiple posttranslational modifications (PTMs) have been documented exist on the same proteins, revealing an additional level of complexity (named “PTM crosstalk”) that, due its dynamic nature, is challenging predict. Here, we propose motif for PTM crosstalk between two most common PTMs: phosphorylation and O-GlcNAcylation. Through use kinetic-based high-resolution mass spectrometry assay, highlight specific residues when phosphorylated, hamper O-GlcNAcylation at nearby sites. In addition, show that Ser/Thr in one kinase motifs, PX(S/T)P, cannot be O-GlcNAcylated, demonstrating reciprocal does not occur with Pro-directed kinases.