Characterization of protein kinase CK2 from Trypanosoma brucei

Bryan C. Jensen, Charles T. Kifer, Deirdre L. Brekken, Amber C. Randall, Qin Wang, Becky L. Drees, Marilyn Parsons

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

CK2 is a ubiquitous but enigmatic kinase. The difficulty in assigning a role to CK2 centers on the fact that, to date, no biologically relevant modulator of its function has been identified. One common theme revolves around a constellation of known substrates involved in growth control, compatible with its concentration in the nucleus and nucleolus. We had previously described the identification of two catalytic subunits of CK2 in Trypanosoma brucei and characterized one of them. Here we report the characterization of the second catalytic subunit, CK2α′, and the identification and characterization of the regulatory subunit CK2β. All three subunits are primarily localized to the nucleolus in T. brucei. We also show that CK2β interacts with the nucleolar protein NOG1, adding to the interaction map which previously linked CK2α to the nucleolar protein NOPP44/46, which in turn associates with the rRNA binding protein p37. CK2 activity has four distinctive features: near equal affinity for GTP and ATP, heparin sensitivity, and stimulation by polyamines and polybasic peptides. Sequence comparison shows that the parasite orthologues have mutations in residues previously mapped as important in specifying affinity for GTP and stimulation by both polyamines and polybasic peptides. Studies of the enzymatic activity of the T. brucei CK2s show that both the affinity for GTP and stimulation by polyamines have been lost and only the features of heparin inhibition and stimulation by polybasic peptides are conserved.

Original languageEnglish (US)
Pages (from-to)28-40
Number of pages13
JournalMolecular and Biochemical Parasitology
Volume151
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • CK2
  • Casein kinase
  • NOG1
  • Nucleolus
  • Protein kinase
  • TAP-tag
  • Trypanosoma

ASJC Scopus subject areas

  • Parasitology
  • Molecular Biology

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