Diverse regulation of AKT and GSK-3β by O-GlcNAcylation in various types of cells

FEBS Lett. 2012 Jul 30;586(16):2443-50. doi: 10.1016/j.febslet.2012.05.063. Epub 2012 Jun 8.


Protein kinase B (AKT) and glycogen synthase kinase-3β (GSK-3β) are major components of insulin-AKT signaling that plays crucial roles in various types of tissue. Recent studies found that these two kinases are modified posttranslationally by O-GlcNAcylation. Here, we demonstrate that O-GlcNAcylation regulated phosphorylation/activation of AKT and GSK-3β in different manners in kidney HEK-293FT cells, but did not affect these two kinases in hepatic HepG2 cells. In neuronal cells, O-GlcNAcylation regulated phosphorylation of AKT negatively, but had no effect on GSK-3β. These results suggest protein-specific and cell type-specific regulation of AKT and GSK-3β by O-GlcNAcylation. Therefore, studies on the roles of AKT and GSK-3β O-GlcNAcylation should be done in a tissue- and cell type-specific manner.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / chemistry*
  • Animals
  • Gene Expression Regulation, Enzymologic*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • HEK293 Cells
  • Hep G2 Cells
  • Hippocampus / metabolism
  • Humans
  • Insulin / metabolism
  • Mice
  • Neurons / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • Tissue Distribution


  • Insulin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
  • Acetylglucosamine