Regulation of the O-linked beta-N-acetylglucosamine transferase by insulin signaling.
O-Linked beta-N-acetylglucosamine (O-GlcNAc) transferase (OGT) catalyzes the addition of O-linked beta-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.
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA.
Stephen A
SA
Whelan
M Daniel
MD
Lane
Gerald W
GW
Hart
D041721:3T3-L1 Cells; D000117:Acetylglucosamine / Q000737:chemistry* / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D007313:Insecta; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009113:Muramidase / Q000737:chemistry; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
D007328:Insulin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D017351:N-Acetylglucosaminyltransferases; D011972:Receptor, Insulin; D019061:src-Family Kinases; D009113:Muramidase; D000117:Acetylglucosamine