Location, location, location: new insights into O -GalNAc protein glycosylation

O -GalNAc glycosylation of proteins confers essential structural, protective and signaling roles in eumetazoans. Addition of O -glycans onto proteins is an extremely complex process that regulates both sites of attachment and the types of oligosaccharides added. Twenty distinct polypeptide GalNAc-transferases (GalNAc-Ts) initiate O -glycosylation and fine-tuning their expression provides a mechanism for regulating this action. Recently, a new mode of regulation has emerged where activation of Src kinase selectively redistributes Golgi-localized GalNAc-Ts to the ER. This relocalization results in a strong increase in the density of O -glycan decoration. In this review, we discuss how different mechanisms can regulate the number and the types of O -glycans decorating proteins. In addition, we speculate how Src-dependent relocation of GalNAc-Ts could play an important role in cancerous cellular transformation.