Premium
O‐GlcNAcylation of Kinases
Author(s) -
Dias Wagner Barbosa,
Hart Gerald W
Publication year - 2007
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.21.6.a985-a
Subject(s) - kinase , phosphorylation , serine , biochemistry , threonine , microbiology and biotechnology , cytosol , signal transduction , protein phosphorylation , biology , chemistry , protein kinase a , enzyme
O‐linked beta‐N‐acetylglucosamine (O‐GlcNAc) is an abundant and dynamic post‐translational modification, similar to phosphorylation, that occurs on serine and threonine residues of cytosolic and nuclear proteins. O‐GlcNAc‐containing proteins are crucial in regulating cellular processes, including signaling, cell cycle, and transcription, among others. O‐GlcNAc has been detected on myriad proteins, including transcription factors, cytoskeletal proteins, nuclear pore proteins, and signal transduction molecules, including some kinases. Kinases represent more than 2% of proteins encoded by the human genome, and are involved in nearly all fundamental cellular processes. Here, we used two different approaches to identify new O‐GlcNAc‐modified kinases. A functional human kinase array revealed 30–40 kinases as good acceptor substrates for O‐GlcNAc transferase in vitro. Reverse‐phase high‐performance liquid chromatography fractionation of O‐GlcNAcylated affinity‐purified ATP‐binding proteins from rat brain shows approximately 20–30 distinct modified proteins. LC‐MS/MS was used to identify these bands as kinases and other ATP‐binding proteins. The confirmation of O‐GlcNAcylation of selected kinases in vivo and the influence of this modification on their activity and function are under investigation. This work is supported by NIH grants CA42486 and HD13563. G.W. H. 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.