Regulation of the O-linked β-N-acetylglucosamine transferase by insulin signaling

Stephen A. Whelan, M. Daniel Lane, Gerald Warren Hart

Research output: Contribution to journalArticle

Abstract

O-Linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) catalyzes the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) onto serine and threonine residues in response to stimuli or stress analogous to phosphorylation by Ser/Thr-kinases. Like protein phosphatases, OGT appears to be targeted to myriad specific substrates by transiently interacting with specific targeting subunits. Here, we show that OGT is activated by insulin signaling. Insulin treatment of 3T3-L1 adipocytes stimulates both tyrosine phosphorylation and catalytic activity of OGT. A subset of OGT co-immunoprecipitates with the insulin receptor. Insulin stimulates purified insulin receptor to phosphorylate OGT in vitro. OGT is a competitive substrate with reduced and carboxyamidomethylated lysozyme (RCAM-lysozyme), a well characterized insulin receptor substrate. Insulin stimulation of 3T3-L1 adipocytes results in a partial translocation of OGT from the nucleus to the cytoplasm. The insulin activation of OGT results in increased O-GlcNAc modification of OGT and other proteins including, signal transducer and activator of transcription 3 (STAT3). We conclude that insulin stimulates the tyrosine phosphorylation and activity of OGT.

Original languageEnglish (US)
Pages (from-to)21411-21417
Number of pages7
JournalJournal of Biological Chemistry
Volume283
Issue number31
DOIs
StatePublished - Aug 1 2008

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Insulin
Phosphorylation
Insulin Receptor
Acetylglucosamine
Adipocytes
Tyrosine
UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase
O-GlcNAc transferase
Substrates
STAT3 Transcription Factor
Phosphoprotein Phosphatases
Threonine
Muramidase
Serine
Catalyst activity
Cytoplasm
Phosphotransferases
Chemical activation
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Regulation of the O-linked β-N-acetylglucosamine transferase by insulin signaling. / Whelan, Stephen A.; Lane, M. Daniel; Hart, Gerald Warren.

In: Journal of Biological Chemistry, Vol. 283, No. 31, 01.08.2008, p. 21411-21417.

Research output: Contribution to journalArticle

Whelan, Stephen A. ; Lane, M. Daniel ; Hart, Gerald Warren. / Regulation of the O-linked β-N-acetylglucosamine transferase by insulin signaling. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 31. pp. 21411-21417.
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