The O‐linked N‐acetylglucosamine modification in cellular signalling and the immune system

The intracellular modification of proteins by the addition of a single O‐linked N‐acetylglucosamine (O‐GlcNAc) molecule is a ubiquitous post‐translational modification in eukaryotic cells. It is catalysed by O‐linked N‐acetylglucosaminyltransferase, which attaches O‐GlcNAc to serine/threonine residues, and it is counter‐regulated by β‐N‐acetylglucosaminidase, which is the antagonistic glycosidase that removes the O‐GlcNAc group. O‐GlcNAc modification competes with phosphorylation by protein kinases at similar sites, thereby affecting important signalling nodes. Accumulating evidence supports a central role for O‐GlcNAc modifications and the corresponding enzymes in the regulation of immune cells, particularly in the activation processes of T and B lymphocytes. Here, we discuss recent advances in the field of O‐GlcNAc modifications, focusing on the cells of the immune system.