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Large scale analysis of synaptic phosphorylation and O‐GlcNAcylation reveals complex interplay between these post‐translational modifications
Author(s) -
Trinidad Jonathan C,
Barkan David T,
Gulledge Brittany,
Thalhammer Agnes,
Sali Andrej,
Schoepfer Ralf,
Burlingame Alma L
Publication year - 2012
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.26.1_supplement.978.2
Subject(s) - phosphorylation , crosstalk , threonine , serine , protein phosphorylation , kinase , microbiology and biotechnology , intracellular , chemistry , biochemistry , biology , protein kinase a , physics , optics
O‐linked N‐acetylglucosamine (O‐GlcNAc) is a dynamic, reversible monosaccharide modifier of serine‐ and threonine‐residues on intracellular protein domains. Crosstalk between O‐GlcNAc and phosphorylation signaling mechanisms has been proposed. However, to date there has not been a large scale evaluation of these two PTMs at endogenous levels in any complex biological system. Here, we identified over 1,750 GlcNAcylation and16,500 phosphorylation sites from the same mouse brain synaptosomes. As has previously been demonstrated for phosphorylation, we show that GlcNAcylation tends to occur in clusters on disordered regions of proteins. However, the distribution of GlcNAcylation sites is virtually random with respect to phosphorylation, suggesting that negative crosstalk at the structural level is not a general phenomenon. We frequently observed proteins extensively phosphorylated with minimal GlcNAcylation. However, proteins extensively GlcNAcylated were almost always phosphorylated to a similar or greater extent, indicating the process of GlcNAcylation appears functionally correlated to phosphorylation.