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Interactions between subunits of protein kinase CK2 and their protein substrates influences its sensitivity to specific inhibitors

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Abstract

Five isoforms of CK2 may exist simultaneously in yeast cells: free catalytic subunits CK2α′, CK2α and three holoenzymatic structures composed of αα′ββ′, α2ββ′ and α′2ββ′. Each isolated and purified form exhibits properties typical for CK2, but they differ in substrate specificity as well as in sensitivity to specific modulators. All five isoforms of protein kinase CK2 from Saccharomyces cerevisiae were examined for their binding capacity with ATP/GTP and two commonly used ATP-competitive inhibitors TBB and TBI. Enzymes were tested with protein substrates differently interacting with CK2 subunits: Elf1, Fip1, Svf1, P2B and synthetic peptide. Obtained results show that K m for ATP varies from 2.4–53 μM for Elf1/CK2α′ and Svf1/CK2α, respectively. Similar differences can be seen in case when GTP was used as phosphate donor. The inhibitory effect depends on composition of CK2/substrate complexes. Highest sensitivity to TBB shows all complexes containing αα′ββ′ isoform with K i values between 0.2 and 1.1 μM. The prospect that TBB and TBI could be utilized to discriminate between different molecular forms of CK2 in yeast cells was examined. Both inhibitors, TBB as well as TBI, decreases cell growth to extents devoting interactions with different CK2 isoforms present in the cell but the presence of β/β′-dimer has a high importance towards sensitivity. Conceivably, a given inhibitor concentration can inhibit only selected CK2-mediated processes in the cell.

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Abbreviations

CK2:

Protein kinase CK2

P2B:

Acidic ribosomal protein P2B

Fip1:

mRNA polyadenylation factor

Svf1:

Survival factor

Elf1:

Transcription elongation factor

SP:

Synthetic peptide (RRRADDSDDDDD)

TBB:

4,5,6,7-Tetrabromo-1H-benzotriazole

TBI:

4,5,6,7-Tetrabromo-1H-benzimidazole

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Authors and Affiliations

  1. Department of Molecular Biology, Institute of Biotechnology, John Paul II Catholic University of Lublin, Kraśnicka Av. 102, 20-718, Lublin, Poland

    Monika Janeczko, Maciej Masłyk, Ryszard Szyszka & Andrea Baier

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  1. Monika Janeczko
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  2. Maciej Masłyk
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  3. Ryszard Szyszka
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  4. Andrea Baier
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Correspondence to Andrea Baier.

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Janeczko, M., Masłyk, M., Szyszka, R. et al. Interactions between subunits of protein kinase CK2 and their protein substrates influences its sensitivity to specific inhibitors. Mol Cell Biochem 356, 121–126 (2011). https://doi.org/10.1007/s11010-011-0951-x

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  • DOI: https://doi.org/10.1007/s11010-011-0951-x

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