Site-specific interplay between O-GlcNAcylation and phosphorylation in cellular regulation

FEBS Lett. 2010 Jun 18;584(12):2526-38. doi: 10.1016/j.febslet.2010.04.044. Epub 2010 Apr 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acetylation
  • Acetylglucosamine / metabolism
  • Acetylglucosaminidase / metabolism
  • Animals
  • Binding Sites
  • Humans
  • Mass Spectrometry
  • Models, Biological
  • Models, Molecular
  • N-Acetylglucosaminyltransferases / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational / physiology*
  • Signal Transduction


  • N-Acetylglucosaminyltransferases
  • Acetylglucosaminidase
  • Acetylglucosamine