Expression and regulation of protein kinase CK2 during the cell cycle

  • Denis G. Bosc
  • Bernhard Lüscher
  • David W. Litchfield
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 27)

Abstract

There are indications from genetic, biochemical and cell biological studies that protein kinase CK2 (formerly casein kinase II) has a variety of functions at different stages in the cell cycle. To further characterize CK2 and its potential roles during cell cycle progression, one of the objectives of this study was to systematically examine the expression of all three subunits of CK2 at different stages in the cell cycle. To achieve this objective, we examined levels of CK2α, CK2α′ and CK2β on immunoblots as well as CK2 activity in samples prepared from: (i) elutriated populations of MANCA (Burkitt lymphoma) cells, (ii) serum-stimulated GL30-92/R (primary human fibroblasts) cells and (iii) drug-arrested chicken bursal lymphoma BK3 A cells. On immunoblots, we observed a significant and co-ordinate increase in the expression of CK2α and CK2α′ following serum stimulation of quiescent human fibroblasts. By comparison, no major fluctuations in CK2 activity were detected during any other stages during the cell cycle. Furthermore, we did not observe any dramatic differences between the relative levels of CK2α to CK2α′ during different stages in the cell cycle. However, we observed a significant increase in the amount of CK2β relative to CK2α in cells arrested with nocodazole. We also examined the activity of CK2 in extracts or in immunoprecipitates prepared from drug-arrested cells. Of particular interest is the observation that the activity of CK2 is not changed in nocodazole-arrested cells. Since CK2 is maximally phosphorylated in these cells, this result suggests that the phosphorylation of CK2 by p34cdc2 does not affect the catalytic activity of CK2. However, the activity of CK2 was increased by incubation with p34cdc2 in vitro. Since this activation was independent of ATP we speculate that p34cdc2 may have an associated factor that stimulates CK2 activity. Collectively, the observations that relative levels of CK2β increase in mitotic cells, that CK2α and CK2β are phosphorylated in mitotic cells and that p34cdc2 affects CK2 activity in vitro suggest that CK2 does have regulatory functions associated with cell division. (Mol Cell Biochem 191: 213–222, 1999)

Key words

protein kinase CK2 (CK2) cell cycle p34cdc2 mitosis CK2 activation cell synchrony 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Allende JE, Allende CC: Protein kinase CK2: An enzyme with multiple Substrates and a puzzling regulation. FASEB J 9: 313–323, 1995PubMedGoogle Scholar
  2. 2.
    Issinger O-G: Casein kinases, pleiotropic mediators of cellular regulation. Pharmacol Ther 59: 1–30, 1993PubMedCrossRefGoogle Scholar
  3. 3.
    Tuazon PT, Traugh JA: Casein Kinase I and II — Multipotential serine protein kinases: Structure, function, and regulation. In: P. Greenard, and G.A. Robinson (eds). Advances in Second Messenger and Phosphoprotein Research, Raven Press, Ltd., New York, 1991,pp 123–164Google Scholar
  4. 4.
    Pinna LA: Casein kinase II: An eminence grise in cellular regulation. Biochim Biophys Acta 1054: 267–284, 1990PubMedCrossRefGoogle Scholar
  5. 5.
    Litchfield DW, Liischer B: Casein Kinase II in signal transduction and cell cycle regulation. Mol Cell Biochem 127/128: 187–199,1993CrossRefGoogle Scholar
  6. 6.
    Lozeman FJ, Litchfield DW, Piening C, Takio K, Walsh KA, Krebs EG: Isolation and characterization of human clones encoding the a anda’ subunits of casein kinase II. Biochemistry 29: 8436–8447,1990PubMedCrossRefGoogle Scholar
  7. 7.
    Litchfield DW, Lüscher B, Lozeman FJ, Eisenman RN, Krebs EG: Phosphorylation of CKII by p34cdc2 in vitro and at mitosis. J Biol Chem 267:13943–13951, 1992PubMedGoogle Scholar
  8. 8.
    Bosc DG, Slominski E, Sichler C, Litchfield DW: Phosphorylation of casein kinase II by p34cdc2: Identification of phosphorylation sites using phosphorylation site mutants in vitro. J Biol Chem 270: 25872–25878, 1995PubMedCrossRefGoogle Scholar
  9. 9.
    Yu IJ, Spector DL, Bae YS, Marshak DR: Immunocytochemical localization of casein kinase II during interphase and mitosis. J Cell Biol 114: 1217–1232, 1991PubMedCrossRefGoogle Scholar
  10. 10.
    Krek W, Maridor G, Nigg EA: Casein kinase II is a predominantly nuclear enzyme. J Cell Biol 116: 43–55, 1992PubMedCrossRefGoogle Scholar
  11. 11.
    Penner CG, Wang Z, Litchfield D: Expression and localization of epitopetagged protein kinase CK2. J Cell Biochem 64: 525–537,1997PubMedCrossRefGoogle Scholar
  12. 12.
    Meggio F, Boldyreff B, Marin O, Pinna LA, Issinger O-G: Role of the β subunit of casein kinase-2 on the stability and specificity of the recombinant reconstituted holoenzyme. Eur J Biochem 204:293–297, 1992PubMedCrossRefGoogle Scholar
  13. 13.
    Lüscher B, Litchfield DW: Biosynthesis of casein kinase II in lymphoid cell lines. Eur J Biochem 220: 521–526, 1994PubMedCrossRefGoogle Scholar
  14. 14.
    Gietz RD, Graham K, Litchfield DW: Interactions between subunits of casein kinase II. J Biol Chem 270: 13017–13021, 1995PubMedCrossRefGoogle Scholar
  15. 15.
    Kusk W, Bendixen C, Duno M, Westergaard, Thomsen B: Genetic dissection of intersubunit contacts within human protein kinase CK2. J Mol Biol 253: 703–711, 1995PubMedCrossRefGoogle Scholar
  16. 16.
    Boldyreff B, Mietens U, Issinger O-G: Structure of protein kinase CK2: Dimerization of the human β-subunit. FEBS Lett 379: 153–156, 1996PubMedCrossRefGoogle Scholar
  17. 17.
    Litchfield DW, Lozeman FA, Cicirelli MF, Harrylock M, Ericsson LH, Piening CA, Krebs EG: Phosphorylation of the β subunit of casein kinase II in human A431 cells. J Biol Chem 266: 20380–20389,1991PubMedGoogle Scholar
  18. 18.
    Boldyreff B, James P, Staudeman W, Issinger O-G: Ser2 is the autophosphorylation site in the β subunit from bicistronically expressed human CK-2 and from native rat liver CK-2β. Eur J Biochem 218: 515–521, 1993PubMedCrossRefGoogle Scholar
  19. 19.
    Litchfield DW, Bosc DG, Slominski E: The protein kinase from mitotic human cells that phosphorylate Ser209 on the casein kinase II β subunit is p34cdc2. Biochim Biophys Acta 13873: 1–10, 1995Google Scholar
  20. 20.
    Hanna DE, Rethinaswamy A, Glover CVC: Casein kinase II is required for cell cycle progression during G1 and G2/M in Saccharomyces cerevisiae. J Biol Chem 270: 25905–25914, 1995PubMedCrossRefGoogle Scholar
  21. 21.
    Pepperkok R, Lorenz P, Jakobi R, Ansorge W, Pyerin W: Cell growth stimulation by EGF. Inhibition through antisense oligonucleotides demonstrates important role of casein kinase II. Exp Cell Res 197: 245–253, 1991PubMedCrossRefGoogle Scholar
  22. 22.
    Pyerin W, Pepperkok R, Ansorge W, Lorenz P: Early cell growth stimulation is inhibited by casein kinase II antisense oligodeoxynucleotides. Ann NY Acad Sci 650: 295–298, 1992CrossRefGoogle Scholar
  23. 23.
    Lorenz P, Pepperkok R, Ansorge W, Pyerin W: Cell biological studies with monoclonal and polyclonal antibodies against human casein II subunit β demonstrate participation of the kinase in mitogenic signalling. J Biol Chem 268: 2733–2739, 1993PubMedGoogle Scholar
  24. 24.
    Pepperkok R, Lorenz P, Ansorge W, Pyerin W: Casein kinase II is required for transition of Go/G1, early G1, and G1/S phases of the cell cycle. J Biol Chem 269: 6986–6991, 1994PubMedGoogle Scholar
  25. 25.
    Carroll D, Marshak DA: Serum-stimulated cell growth causes oscillations in casein kinase II activity. J Biol Chem 264: 7345–7348, 1989PubMedGoogle Scholar
  26. 26.
    Marshak DR, Russo GL: Regulation of protein kinase CKII during the cell division cycle. Cell Mol Biol Res 40: 513–517, 1994PubMedGoogle Scholar
  27. 27.
    Schmidt-Spaniol L, Grimm B, Issinger O-G: Subcellular localization of protein kinase CK-2 a-and β-subunits in synchronized cells from primary human fibroblasts and established cell lines. Cell Mol Biol Res 39: 761–772, 1993PubMedGoogle Scholar
  28. 28.
    Litchfield DW, Lozeman FJ, Piening C, Sommercorn J, Takio K, Walsh KA, Krebs EG: Subunit structure of casein kinase II from bovine testis: Demonstration that the α and α′ subunits are distinct polypeptides. J Biol Chem 265: 7638–7644, 1990PubMedGoogle Scholar
  29. 29.
    Mulner-Lorillon O, Cormier P, Labbe JC, Doree M, Poulhe R, Osborne H, Belle R: M-phase specific cdc2 protein kinase phosphorylates the β subunit of casein kinase II and increases casein kinase II activity. Eur J Biochem 193: 529–534, 1990PubMedCrossRefGoogle Scholar
  30. 30.
    Meggio F, Boldyreff B, Marin O, Issinger O-G, Pinna LA: Phosphorylation and activation of protein kinase CK2 by p34cdc2 are independent events. Eur J Biochem 230: 1025–1031, 1995PubMedCrossRefGoogle Scholar
  31. 31.
    Filhol-Cochet O, Loue-Mackenbach P, Cochet C, Chambaz EM: Casein kinase 2 and the cell response to growth factors. Cell Mol Biol Res 40: 529–537, 1994PubMedGoogle Scholar
  32. 32.
    Tawfic S, Ahmed K: Growth stimulus-mediated differential translocation of casein kinase II to the nuclear matrix. J Biol Chem 269: 24615–24620, 1994PubMedGoogle Scholar
  33. 33.
    Litchfield DW, Dobrowolska G, Krebs EG: Regulation of casein kinase II by growth factors: A re-evaluation. Cell Mol Biol Res 40: 373–381, 1994PubMedGoogle Scholar
  34. 34.
    Chen M, Li D, Krebs EG, Cooper J: The casein kinase II β subunit binds to Mos and inhibits Mos activity. Mol Cell Biol 17: 1904–1912, 1997PubMedGoogle Scholar
  35. 35.
    Boldyreff B, Issinger O-G: A-Raf kinase is a new interacting partner of protein kinase CK2 beta subunit. FEBS Lett 403: 197–199, 1997PubMedCrossRefGoogle Scholar
  36. 36.
    Hageman C, Kalmes A, Wixier V, Wixier L, Schuster T, Rapp UR: The regulatory subunit of protein kinase CK2 is a specific A-Raf activator. FEBS Lett 403: 200–202, 1997CrossRefGoogle Scholar
  37. 37.
    Chen M, Cooper JA: The beta subunit of CKII negatively regulates Xenopus oocyte maturation. Proc Natl Acad Sci USA 94: 9136–9140,1997PubMedCrossRefGoogle Scholar
  38. 38.
    Roussou L, Draetta G: The Scizosaccharomyces pombe casein kinase II a and β subunits: Evolutionary conservation and positive role of the p subunit. Mol Cell Biol 14: 576–586, 1994PubMedGoogle Scholar
  39. 39.
    Norbury C, Nurse P: Animal cell cycles and their control. Annu Rev Biochem 61: 441–470, 1992PubMedCrossRefGoogle Scholar
  40. 40.
    Cardenas ME, Dang O, Glover CVC, Gasser SM: Casein kinase II phosphorylates the eukaryote-specific C-terminal domani of topo-isomerase II in vivo. EMBO J 11: 1785–1796, 1992PubMedGoogle Scholar
  41. 41.
    Kimura Y, Rutherford SL, Miyata Y, Yahara I, Freeman B, Yue L, Morimoto RI, Lindquist S: Cdc37 is a molecular chaperone with specific functions in signal transduction. Genes Dev 11: 1775–1785, 1997PubMedCrossRefGoogle Scholar
  42. 42.
    McCann R, Glover CVC: Evidence for the physiological interaction of yeast Cdc37 and casein kinase II. Mol Biol Cell (Supp) 6: 133a, 1995Google Scholar
  43. 43.
    Stepanova L, Leng X, Parker SR, Harper JW: Mammalian p50cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev 10: 1491–1502, 1996PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1999

Authors and Affiliations

  • Denis G. Bosc
    • 1
  • Bernhard Lüscher
    • 2
  • David W. Litchfield
    • 3
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of ManitobaWinnipegCanada
  2. 2.Institut für MolekularbiologieMedizinische Hochschule HannoverHannoverGermany
  3. 3.Department of Biochemistry, Health Sciences CentreUniversity of Western OntarioLondonCanada

Personalised recommendations