Crosstalk between phosphorylation and O‐Glc NA cylation: friend or foe

• Published in: The FEBS journal 2018-09, Vol.285 (17), p.3152-3167
• Main Authors: van der Laarse, Saar A. M., Leney, Aneika C., Heck, Albert J. R.
• Format: Article
• Language: English
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.14491

A wide variety of protein post‐translational modifications ( PTM s) decorate cellular proteins, regulating their structure, interactions and ultimately their function. The density of co‐occurring PTM s on proteins can be very high, where multiple PTM s can positively or negatively influence each other's actions, termed PTM crosstalk. In this review, we highlight recent progress in the area of PTM crosstalk, whereby we focus on crosstalk between protein phosphorylation and O‐Glc NA cylation. These two PTM s largely target identical (i.e., Ser and Thr) amino acids in proteins. Phosphorylation/O‐Glc NA cylation crosstalk comes in many flavors, for instance by competition for the same site/residue (reciprocal crosstalk), as well as by modifications influencing each other in proximity or even distal on the protein sequence. PTM crosstalk is observed on the writers of these modifications (i.e., kinases and O‐Glc NA c transferase), on the erasers (i.e., phosphatases and O‐Glc NA case), and on the readers and the substrates. We describe examples of all these different flavors of crosstalk, and additionally the methods that are emerging to better investigate in particular phosphorylation/O‐Glc NA cylation crosstalk.