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The alpha2 catalytic subunit of AMP‐activated protein kinase (AMPK) is O‐GlcNAc modified
Author(s) -
Bullen John William,
Hart Gerald
Publication year - 2008
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.22.1_supplement.614.7
Subject(s) - ampk , protein kinase a , phosphorylation , chemistry , protein subunit , amp activated protein kinase , acetyl coa carboxylase , pyruvate carboxylase , immunoprecipitation , kinase , biochemistry , microbiology and biotechnology , energy homeostasis , flux (metallurgy) , enzyme , biology , gene , receptor , organic chemistry
O‐linked N‐acetylglucosamine (O‐GlcNAc) is a highly dynamic Ser/Thr specific protein modification often occurring at the same or adjacent sites as phosphorylation. Increased flux through the hexosamine biosynthetic pathway (HBP) elevates protein O‐GlcNAcylation and causes insulin resistance. Recent studies in adipocytes showed that chronic hexosamine flux through the HBP activates fatty‐acid oxidation through AMP‐activated kinase (AMPK), a vital sensor and regulator of whole body and cellular energy homeostasis. They further suggest that AMPK, or a binding partner, may be O‐GlcNAc modified in adipocytes. Using O‐GlcNAcylated protein specific immunoblotting and enzymatic radioactive labeling experiments, we conclusively show that immunoprecipitated AMPKα2 is itself O‐GlcNAc modified in two different cell types. Furthermore, global elevation of O‐GlcNAcylated protein in C2C12 muscle cells increases AMPKα2 protein levels, but in contrast to adipocytes, decreases phosphorylation of its primary downstream target, acetyl‐CoA carboxylase (ACC). We are currently site mapping O‐GlcNAcylated sites on AMPKα2, as well as investigating further the role O‐GlcNAc may have on tissue‐specific regulation of AMPK activity. (Supported by NIH grant R01 DK61671. Dr. Hart receives a share of royalty received by the university on sales of the CTD 110.6 antibody. Terms of this arrangement are managed by JHU).