Regulation of CK2 by phosphorylation and O-GlcNAcylation revealed by semisynthesis

Mary Katherine Tarrant, Hee Sool Rho, Zhi Xie, Yu Lin Jiang, Christopher Gross, Jeffrey C. Culhane, Gai Yan, Jiang Qian, Yoshitaka Ichikawa, Tatsuji Matsuoka, Natasha Zachara, Felicia A. Etzkorn, Gerald W. Hart, Jun Seop Jeong, Seth Blackshaw, Heng Zhu, Philip A. Cole

Research output: Contribution to journalArticlepeer-review


Protein serine-threonine kinase casein kinase II (CK2) is involved in a myriad of cellular processes including cell growth and proliferation through its phosphorylation of hundreds of substrates, yet how CK2 function is regulated is poorly understood. Here we report that the CK2 catalytic subunit CK2α is modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) on Ser347, proximal to a cyclin-dependent kinase phosphorylation site (Thr344). We use protein semisynthesis to show that phosphorylation of Thr344 increases the cellular stability of CK2α by strengthening its interaction with Pin1, whereas glycosylation of Ser347 seems to be antagonistic to Thr344 phosphorylation and permissive to proteasomal degradation. By performing kinase assays with site-specifically phospho- and glyco-modified CK2α in combination with CK2β and Pin1 binding partners on human protein microarrays, we show that the kinase substrate selectivity of CK2 is modulated by these specific post-translational modifications. This study suggests how a promiscuous protein kinase can be regulated at multiple levels to achieve particular biological outputs.

Original languageEnglish (US)
Pages (from-to)262-269
Number of pages8
JournalNature chemical biology
Issue number3
StatePublished - Mar 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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