title: Site-specific interplay between O-GlcNAcylation and phosphorylation in cellular regulation.
abstract: Ser(Thr)-O-linked beta-N-acetylglucosamine (O-GlcNAc) is a ubiquitous modification of nucleocytoplasmic proteins. Extensive crosstalk exists between O-GlcNAcylation and phosphorylation, which regulates signaling in response to nutrients/stress. The development of novel O-GlcNAc detection and enrichment methods has improved our understanding of O-GlcNAc functions. Mass spectrometry has revealed O-GlcNAc's many interactions with phosphorylation-mediated signaling. However, mechanisms regulating O-GlcNAcylation and phosphorylation are quite different. Phosphorylation is catalyzed by hundreds of distinct kinases. In contrast, in mammals, uridine diphospho-N-acetylglucosamine:polypeptide beta-N-acetylglucosaminyl transferase (OGT) and beta-D-N-acetylglucosaminidase (OGA) are encoded by single highly conserved genes. Both OGT's and OGA's specificities are determined by their transient associations with many other proteins to create a multitude of specific holoenzymes. The extensive crosstalk between O-GlcNAcylation and phosphorylation represents a new paradigm for cellular signaling.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University, School of Medicine, Baltimore, MD 21205-2185, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.forename: Shino
authors.initials: S
authors.lastname: Shimoji
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Hart
mesh_terms: D000107:Acetylation; D000117:Acetylglucosamine / Q000378:metabolism; D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D006801:Humans; D013058:Mass Spectrometry; D008954:Models, Biological; D008958:Models, Molecular; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D017351:N-Acetylglucosaminyltransferases; D000118:Acetylglucosaminidase; D000117:Acetylglucosamine