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Differential substrate selectivity and stability with different forms of protein kinase CK2
Author(s) -
Tarrant Mary Katherine,
Rho HeeSool,
Xie Zhi,
Qian Jiang,
Zhu Heng,
Cole Philip A.
Publication year - 2011
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.25.1_supplement.lb146
Subject(s) - casein kinase 2 , phosphorylation , protein kinase a , protein subunit , chemistry , biochemistry , kinase , protein phosphorylation , microbiology and biotechnology , map2k7 , autophagy related protein 13 , mitogen activated protein kinase kinase , cyclin dependent kinase 2 , biology , gene
Protein Kinase CK2 is a highly conserved, constitutively active protein kinase with over 300 known substrates that plays a key role in cell proliferation. Others have shown that CK2 is post‐translationally modified on its C‐terminal tail with phosphorylation and O ‐linked GlcNAc sites. To determine the role of these modifications on the regulation of CK2, we used protein semisynthesis techniques to generate homogenous samples of CK2α possessing the site‐specific post‐translational modifications or non‐hydrolyzable mimics of these modifications. Phosphorylation of CK2α at Thr344 enhances it cellular stability and the presence of O ‐GlcNAc at Ser347 decreases the extent to which Thr344 on CK2α is phosphorylated. This enhanced cellular stability requires the phosphorylation‐dependent interactions with Pin1 protein. Inhibiting phosphorylation of CK2α or increasing the extent to which CK2α is O ‐GlcNAc‐modified both result in a decrease in CK2α protein levels in cells. Kinase assays on human proteome microarray chips with the semisynthetic CK2 proteins bearing different modifications indicate that these modifications, in addition to the β regulatory subunit, lend substrate selectivity to the kinase for some of its substrates.