Tissue-Specific Functions and Regulation of Protein Kinase CK2

  • Sabrina Welker
  • Christina Servas
  • Meng Rui
  • Claudia Götz
  • Mathias Montenarh
Chapter
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 12)

Abstract

CK2 is a ubiquitously expressed protein kinase which seems to be required for the viability of cells. An increasing number of CK2 substrates raise the questions how CK2 can phosphorylate so many different substrates and how these phosphorylation reactions are regulated. One key answer to these questions seems to be the subcellular localization of CK2 and its individual subunits. Here, we have addressed another strategy for the regulation of CK2, i.e. a tissue-specific expression, subcellular localization and tissue-specific substrates. In the case of pancreatic β-cells, we show that there is a hormonal impact by insulin which is similar to the hormonal regulation by androgens in prostate cancer cells. Furthermore, the subcellular localization of CK2 is specifically regulated by the metabolic status, i.e. glucose concentration in the pancreatic β-cells. Also the enzymatic activity as well as the binding to a pancreas-specific transcription factor Pdx-1 is modulated by the glucose concentration in pancreatic β-cells. Furthermore, the CK2 kinase activity seems to be an important survival factor for pancreatic β-cells. Thus, one key for the understanding of the pleiotropic effects of CK2 seems to be the determination of the regulation of CK2 in specific tissues.

Keywords

Protein kinase CK2 Phosphorylation Pancreas Islet Beta cells Transcription factor 

References

  1. 1.
    Burnett G, Kennedy EP (1954) The enzymatic phosphorylation of proteins. J Biol Chem 211:969–980PubMedGoogle Scholar
  2. 2.
    Gietz RD, Graham KC, Litchfield DW (1995) Interactions between the subunits of casein kinase II. J Biol Chem 270:13017–13021CrossRefPubMedGoogle Scholar
  3. 3.
    Litchfield DW, Slominski E, Lewenza S, Narvey M, Bosc DG, Gietz RD (1996) Analysis of interactions between the subunits of protein kinase CK2. Biochem Cell Biol 74:541–547CrossRefPubMedGoogle Scholar
  4. 4.
    Litchfield DW (2003) Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J 369:1–15CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Bosc DG, Slominski E, Sichler C, Litchfield DW (1995) Phosphorylation of casein kinase II by p34cdc2—Identification of phosphorylation sites using phosphorylation site mutants in vitro. J Biol Chem 270:25872–25878CrossRefPubMedGoogle Scholar
  6. 6.
    Litchfield DW, Lüscher B, Lozeman FJ, Eisenman RN, Krebs E (1992) Phosphorylation of CK II by p34cdc2 in vitro and at mitosis. J Biol Chem 267:13943–13951PubMedGoogle Scholar
  7. 7.
    Litchfield DW, Lozeman FJ, Cicirelli MF, Harrylock M, Ericsson LH, Piening CJ, Krebs EG (1991) Phosphorylation of the beta subunit of casein kinase II in human A431 cells. Identification of the autophosphorylation site and a site phosphorylated by p34cdc2. J Biol Chem 266:20380–20389PubMedGoogle Scholar
  8. 8.
    Ackerman P, Glover CV, Osheroff N (1990) Stimulation of casein kinase II by epidermal growth factor: relationship between the physiological activity of the kinase and the phosphorylation state of its beta subunit. Proc Natl Acad Sci U S A 87:821–825CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Mulner-Lorillon O, Cormier P, Labbe J-C, Doree M, Pouhle R, Osborne H, Belle R (1990) M-phase-specific cdc2 protein kinase phosphorylates the β subunit of casein kinase II and increases casein kinase II activity. Eur J Biochem 193:529–534CrossRefPubMedGoogle Scholar
  10. 10.
    Carroll D, Santoro N, Marshak DR (1988) Regulating cell growth: casein-kinase-II-dependent phosphorylation of nuclear oncoproteins. Cold Spring Harb Symp Quant Biol 53(Pt 1):91–95CrossRefPubMedGoogle Scholar
  11. 11.
    Lolli G, Pinna LA, Battistutta R (2012) Structural determinants of protein kinase CK2 regulation by autoinhibitory polymerization. ACS Chem Biol 7:1158–1163CrossRefPubMedGoogle Scholar
  12. 12.
    Niefind K, Battistutta R (2013) Structural bases protein kinase CK2 function and inhibition. In: Pinna LA (ed) Protein kinase CK2. John Wiley & Sons Inc., Hoboken, NJ, pp 3–75Google Scholar
  13. 13.
    Niefind K, Guerra B, Ermakowa I, Issinger OG (2001) Crystal structure of human protein kinase CK2: insights into basic properties of the CK2 holoenzyme. EMBO J 20:5320–5331CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Niefind K, Raaf J, Issinger OG (2009) Protein kinase CK2: from structures to insights. Cell Mol Life Sci 66:1800–1816CrossRefPubMedGoogle Scholar
  15. 15.
    Glover CVC (1998) On the physiological role of casein kinase II in Saccharomyces cerevisiae. Prog Nucleic Acid Res Mol Biol 59:95–133CrossRefPubMedGoogle Scholar
  16. 16.
    Rethinaswamy A, Birnbaum MJ, Glover CVC (1998) Temperature-sensitive mutations of the CAK1 gene reveal a role for casein kinase II in maintenance of cell polarity in Saccharomyces cerevisiae. J Biol Chem 273:5869–5877CrossRefPubMedGoogle Scholar
  17. 17.
    Buchou T, Vernet M, Blond O, Jensen HH, Pointu H, Olsen BB, Cochet C, Issinger OG, Boldyreff B (2003) Disruption of the regulatory β subunit of protein kinase CK2 in mice leads to a cell-autonomous defect and early embryonic lethality. Mol Cell Biol 23:908–915CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Lou DY, Dominguez I, Toselli P, Landesman-Bollag E, O’Brien C, Seldin DC (2008) The alpha catalytic subunit of protein kinase CK2 is required for mouse embryonic development. Mol Cell Biol 28:131–139CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Xu X, Toselli PA, Russell LD, Seldin DC (1999) Globozoospermia in mice lacking the casein kinase II α′ catalytic subunit. Nat Genet 23:118–121CrossRefPubMedGoogle Scholar
  20. 20.
    Escalier D, Silvius D, Xu X (2003) Spermatogenesis of mice lacking CK2α′: Failure of germ cell survival and characteristic modifications of the spermatid nucleus. Mol Reprod Dev 66:190–201CrossRefPubMedGoogle Scholar
  21. 21.
    Kuenzel EA, Mulligan JA, Sommercorn J, Krebs EG (1987) Substrate specificity determinants for casein kinase II as deduced from studies with synthetic peptides. J Biol Chem 262:9136–9140PubMedGoogle Scholar
  22. 22.
    Salvi M, Sarno S, Cesaro L, Nakamura H, Pinna LA (2009) Extraordinary pleiotropy of protein kinase CK2 revealed by weblogo phosphoproteome analysis. Biochim Biophys Acta 1793:847–859CrossRefPubMedGoogle Scholar
  23. 23.
    Meggio F, Pinna LA (2003) One-thousand-and-one substrates of protein kinase CK2? FASEB J 17:349–368CrossRefPubMedGoogle Scholar
  24. 24.
    Litchfield DW, Dobrowolska G, Krebs EG (1994) Regulation of casein kinase II by growth factors: a reevaluation. Cell Mol Biol Res 40:373–381PubMedGoogle Scholar
  25. 25.
    Hathaway GM, Traugh JA (1982) Casein kinases—multipotential protein kinases. Curr Top Cell Regul 21:101–127CrossRefPubMedGoogle Scholar
  26. 26.
    Montenarh M (2010) Cellular regulators of protein kinase CK2. Cell Tissue Res 342:139–146CrossRefPubMedGoogle Scholar
  27. 27.
    Montenarh M (2003) Protein kinase CK2: in search for its regulation. Adv Clin Exp Med 12:15–22Google Scholar
  28. 28.
    Montenarh M, Götz C (2013) The interactome of protein kinase CK2. In: Pinna LA (ed) Protein kinase CK2. John Wiley & Sons Inc., Hoboken, NJ, pp 76–116CrossRefGoogle Scholar
  29. 29.
    Guerra B, Boldyreff B, Sarno S, Cesaro L, Issinger OG, Pinna LA (1999) CK2: A protein kinase in need of control. Pharmacol Ther 82:303–313CrossRefPubMedGoogle Scholar
  30. 30.
    Faust M, Montenarh M (2000) Subcellular localization of protein kinase CK2: a key to its function? Cell Tissue Res 301:329–340CrossRefPubMedGoogle Scholar
  31. 31.
    Maridor G, Park W, Krek W, Nigg EA (1991) Casein kinase II. cDNA sequences, developmental expression, and tissue distribution of mRNAs for alpha, alpha′, and beta subunits of the chicken enzyme. J Biol Chem 266:2362–2368PubMedGoogle Scholar
  32. 32.
    Mestres P, Boldyreff B, Ebensperger C, Hameister H, Issinger O-G (1994) Expression of casein kinase 2 during mouse embryogenesis. Acta Anat 149:13–20CrossRefPubMedGoogle Scholar
  33. 33.
    Diaz-Nido J, Mizuno K, Nawa H, Marshak DR (1994) Regulation of protein kinase Ck2 isoform expression during rat brain development. Cell Mol Biol Res 40:581–585PubMedGoogle Scholar
  34. 34.
    Diaz-Nido J, Armes-Portela R, Avila J (1992) Increase in cytoplasmic casein kinase II-type activity accompanies neurite growth after DNA synthesis. J Neurochem 587:1820–1828CrossRefGoogle Scholar
  35. 35.
    Ulloa L, Diaz-Nido J, Avila J (1993) Depletion of casein kinase II by antisense oligonucleotide prevents neuritogenesis in neuroblastoma cells. EMBO J 12:1633–1640PubMedCentralPubMedGoogle Scholar
  36. 36.
    Yutani Y, Tei Y, Yukioka M, Inoue A (1982) Occurrence of NI and NII type protein kinases in the nuclei from various tissues of the rat. Arch Biochem Biophys 218:409–420CrossRefPubMedGoogle Scholar
  37. 37.
    Singh TJ, Huang K (1985) Glycogen synthase (casein) kinase I: tissue distribution and subcellular localization. FEBS Lett 190:84–88CrossRefPubMedGoogle Scholar
  38. 38.
    Guerra B, Siemer S, Boldyreff B, Issinger OG (1999) Protein kinase CK2: evidence for a protein kinase CK2β subunit fraction, devoid of the catalytic CK2α subunit, in mouse brain and testicles. FEBS Lett 462:353–357CrossRefPubMedGoogle Scholar
  39. 39.
    Nakajo S, Hagiwara T, Nakajo K, Nakamura Y (1986) Tissue distribution of casein kinases. Biochem Int 13:701–707PubMedGoogle Scholar
  40. 40.
    Girault A-J, Hemmings HC, Zorn SH, Gustafson EL, Greengard P (1990) Characterization in mammalian brain of a DARPP-32 serine kinase identical to casein kinase II. J Neurochem 55:1772–1783CrossRefPubMedGoogle Scholar
  41. 41.
    Stalter G, Siemer S, Becht E, Ziegler M, Remberger K, Issinger O-G (1994) Asymmetric expression of protein kinase CK2 in human kidney tumors. Biochem Biophys Res Commun 202:141–147CrossRefPubMedGoogle Scholar
  42. 42.
    Blanquet PR (2000) Casein kinase 2 as a potentially important enzyme in the nervous system. Prog Neurobiol 60:211–246CrossRefPubMedGoogle Scholar
  43. 43.
    Moreno FJ, Díaz-Nido J, Jiménez JS, Avila J (1999) Distribution of CK2, its substrate MAP1B and phosphatases in neuronal cells. Mol Cell Biochem 191:201–205CrossRefPubMedGoogle Scholar
  44. 44.
    De Camilli P, Greengard P (1986) Synapsin I: a synaptic vesicle-associated neuronal phosphoprotein. Biochem Pharmacol 35:4349–4357CrossRefPubMedGoogle Scholar
  45. 45.
    Martin ME, Alcazar A, Salinas M (1990) Subcellular and regional distribution of casein kinase II and initiation factor 2 activities during rat brain development. Int J Dev Neurosci 8:47–54CrossRefPubMedGoogle Scholar
  46. 46.
    Iimoto DS, Masliah E, Deteresa R, Terry RD, Saitoh T (1990) Aberrant casein kinase II in Alzheimer’s disease. Brain Res 507:273–280CrossRefPubMedGoogle Scholar
  47. 47.
    Masliah E, Iimoto DS, Mallory M, Albright T, Hansen L, Saitoh T (1992) Casein kinase II alteration precedes tau accumulation in tangle formation. Am J Pathol 140:263–268PubMedCentralPubMedGoogle Scholar
  48. 48.
    Baum L, Masliah E, Iimoto DS, Hansen LA, Halliday WC, Saitoh T (1992) Casein kinase II is associated with neurofibrillary tangles but is not an intrinsic component of paired helical filaments. Brain Res 573:126–132CrossRefPubMedGoogle Scholar
  49. 49.
    Jin LW, Saitoh T (1995) Changes in protein kinases in brain aging and Alzheimer’s disease. Implications for drug therapy. Drugs Aging 6:136–149CrossRefPubMedGoogle Scholar
  50. 50.
    Ryu MY, Kim DW, Arima K, Mouradian MM, Kim SU, Lee G (2007) Localization of CKII beta subunits in Lewy bodies of Parkinson’s disease. J Neurol Sci 266:9–12CrossRefPubMedGoogle Scholar
  51. 51.
    Huillard E, Ziercher L, Blond O, Wong M, Deloulme JC, Souchelnytskyi S, Baudier J, Cochet C, Buchou T (2010) Disruption of CK2beta in embryonic neural stem cells compromises proliferation and oligodendrogenesis in the mouse telencephalon. Mol Cell Biol 30:2737–2749CrossRefPubMedCentralPubMedGoogle Scholar
  52. 52.
    Ahmed K, Ishida H (1971) Effect of testosterone on nuclear phosphoproteins of rat ventral prostate. Mol Pharmacol 7:323–327PubMedGoogle Scholar
  53. 53.
    Ahmed K, Tawfic S (1994) Mechanism of intracellular regulation of protein kinase CK2: role of stimulus-mediated subnuclear association. Cell Mol Biol Res 40:539–545PubMedGoogle Scholar
  54. 54.
    Ahmed K, Yenice S, Davis A, Goueli SA (1993) Association of casein kinase 2 with nuclear chromatin in relation to androgenic regulation of rat prostate. Proc Natl Acad Sci U S A 90:4426–4430CrossRefPubMedCentralPubMedGoogle Scholar
  55. 55.
    Yu SH, Wang HM, Davis A, Ahmed K (2001) Consequences of CK2 signaling to the nuclear matrix. Mol Cell Biochem 227:67–71CrossRefPubMedGoogle Scholar
  56. 56.
    Zhang S, Kim KH (1997) Protein kinase CK2 down-regulates glucose-activated expression of the acetyl-CoA carboxylase gene. Arch Biochem Biophys 338:227–232CrossRefPubMedGoogle Scholar
  57. 57.
    Sommercorn J, Mulligan JA, Lozeman FJ, Krebs E (1987) Activation of casein kinase II in response to insulin and to epidermal growth factor. Proc Natl Acad Sci U S A 84:8834–8838CrossRefPubMedCentralPubMedGoogle Scholar
  58. 58.
    Sommercorn J, Krebs EG (1987) Induction of casein kinase II during differentiation of 3T3-L1 cells. J Biol Chem 262:3839–3843PubMedGoogle Scholar
  59. 59.
    Meng R, Götz C, Montenarh M (2010) The role of protein kinase CK2 in the regulation of the insulin production of pancreatic islets. Biochem Biophys Res Commun 401:203–206CrossRefPubMedGoogle Scholar
  60. 60.
    Meng R, Al-Quobaili F, Müller I, Götz C, Thiel G, Montenarh M (2010) CK2 phosphorylation of Pdx-1 regulates its transcription factor activity. Cell Mol Life Sci 67:2481–2489CrossRefPubMedGoogle Scholar
  61. 61.
    Welker S, Götz C, Servas C, Laschke MW, Menger MD, Montenarh M (2013) Glucose regulates protein kinase CK2 in pancreatic ß-cells and its interaction with PDX-1. Int J Biochem Cell Biol 45:2786–2795CrossRefPubMedGoogle Scholar
  62. 62.
    Horoszewicz JS, Leong SS, Kawinski E, Karr JP, Rosenthal H, Chu TM, Mirand EA, Murphy GP (1983) LNCaP model of human prostatic carcinoma. Cancer Res 43:1809–1818PubMedGoogle Scholar
  63. 63.
    Bussolino F, De RM, Sica A, Colotta F, Wang JM, Bocchietto E, Padura IM, Bosia A, DeJana E, Mantovani A (1991) Murine endothelioma cell lines transformed by polyoma middle T oncogene as target for and producers of cytokines. J Immunol 147:2122–2129PubMedGoogle Scholar
  64. 64.
    Martel V, Filhol O, Nueda A, Gerber D, Benitez MJ, Cochet C (2001) Visualization and molecular analysis of nuclear import of protein kinase CK2 subunits in living cells. Mol Cell Biochem 227:81–90CrossRefPubMedGoogle Scholar
  65. 65.
    Theis-Febvre N, Martel V, Laudet B, Souchier C, Grunwald D, Cochet C, Filhol O (2005) Highlighting protein kinase CK2 movement in living cells. Mol Cell Biochem 274:15–22CrossRefPubMedGoogle Scholar
  66. 66.
    Tawfic S, Ahmed K (1994) Growth stimulus-mediated differential translocation of casein kinase 2 to the nuclear matrix. Evidence based on androgen action in the prostate. J Biol Chem 269:24615–24620PubMedGoogle Scholar
  67. 67.
    Yenice S, Davis AT, Goueli SA, Akdas A, Limas C, Ahmed K (1994) Nuclear casein kinase 2 (CK-2) acitivity in human normal, benign hyperplastic, and cancerous prostate. Prostate 24:11–16CrossRefPubMedGoogle Scholar
  68. 68.
    Ahmad KA, Wang G, Unger G, Slaton J, Ahmed K (2008) Protein kinase CK2- A key suppressor of apoptosis. Adv Enzyme Regul 48:179–187CrossRefPubMedCentralPubMedGoogle Scholar
  69. 69.
    Trembley JH, Wu J, Unger GM, Kren BT, Ahmed K (2013) CK2 suppression of apoptosis and its implication in cancer biology and therapy. In: Pinna LA (ed) Protein kinase CK2. John Wiley & Sons Inc., Hoboken, NJ, pp 319–343CrossRefGoogle Scholar
  70. 70.
    Intemann J, Saidu NEB, Schwind L, Montenarh M (2014) ER stress signaling in ARPE-19 cells after inhibition of protein kinase CK2 by CX-4945. Cell Signal 26:1567–1575CrossRefPubMedGoogle Scholar
  71. 71.
    Horoszewicz JS, Leong SS, Chu TM, Wajsman ZL, Friedman M, Papsidero L, Kim U, Chai LS, Kakati S, Arya SK, Sandberg AA (1980) The LNCaP cell line–a new model for studies on human prostatic carcinoma. Prog Clin Biol Res 37:115–132PubMedGoogle Scholar
  72. 72.
    Faust M, Schuster N, Montenarh M (1999) Specific binding of protein kinase CK2 catalytic subunits to tubulin. FEBS Lett 462:51–56CrossRefPubMedGoogle Scholar
  73. 73.
    Asfari M, Janjic D, Meda P, Li G, Halban PA, Wollheim CB (1992) Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines. Endocrinology 130:167–178PubMedGoogle Scholar
  74. 74.
    Ishihara H, Asano T, Tsukuda K, Katagiri H, Inukai K, Anai M, Kikuchi M, Yazaki Y, Miyazaki JI, Oka Y (1993) Pancreatic beta cell line MIN6 exhibits characteristics of glucose metabolism and glucose-stimulated insulin secretion similar to those of normal islets. Diabetologia 36:1139–1145CrossRefPubMedGoogle Scholar
  75. 75.
    Efrat S (1999) Genetically engineered pancreatic beta-cell lines for cell therapy of diabetes. Ann N Y Acad Sci 875:286–293CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Sabrina Welker
    • 1
  • Christina Servas
    • 1
  • Meng Rui
    • 1
  • Claudia Götz
    • 1
  • Mathias Montenarh
    • 1
  1. 1.Medizinische Biochemie und MolekularbiologieUniversität des SaarlandesHomburgGermany

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