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Insulin increases tyrosine phosphorylation and activity of O‐GlcNAc Transferase (OGT)
Author(s) -
Whelan Stephen A,
Hart Gerald W.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a955-d
Subject(s) - phosphorylation , tyrosine phosphorylation , insulin resistance , serine , insulin receptor , insulin , kinase , microbiology and biotechnology , threonine , chemistry , protein subunit , biochemistry , biology , endocrinology , gene
OGT is responsible for the addition of the post‐translational modification O‐GlcNAc onto serine and threonine residues in response to stimuli similar to the addition of phosphorylation by kinases. However, unlike kinases there is only one known catalytic subunit in mammals with several splice variants that non‐covalently interact with a multitude of specific targeting subunits to specifically modify hundreds to thousands of nucleocytoplasmic proteins. The levels of O‐GlcNAc on nucleocytoplasmic proteins change rapidly in response to stress, during the cell cycle, in response to nutrients, and many other signaling events. In addition, increased O‐GlcNAcylation is associated with the onset of insulin resistance in muscle and adipocytes. Here we show that tyrosine phosphorylation of OGT and its catalytic activity are stimulated by insulin treatment of NIH 3T3‐L1 adipocytes. Upon insulin stimulation the OGT interaction profile with other proteins also changes. Control of OGT activity and protein‐protein interactions by insulin signaling may play an important regulatory role in insulin responsive cells and may have a function in the onset of insulin resistance. Supported by NIH grant DK61671 and NIH contract N01‐HV‐28180. G.W. H. receives a share of royalty received by the university on sales of the CTD 110.6 antibody. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.