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Protein Kinase CK2 Cellular Function in Normal and Disease States pp 109–123Cite as

Tissue-Specific Functions and Regulation of Protein Kinase CK2

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Part of the book series: Advances in Biochemistry in Health and Disease ((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.

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References

  1. Burnett G, Kennedy EP (1954) The enzymatic phosphorylation of proteins. J Biol Chem 211:969–980

    CAS  PubMed  Google Scholar 

  2. Gietz RD, Graham KC, Litchfield DW (1995) Interactions between the subunits of casein kinase II. J Biol Chem 270:13017–13021

    Article  CAS  PubMed  Google Scholar 

  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 74:541–547

    Article  CAS  PubMed  Google Scholar 

  4. Litchfield DW (2003) Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J 369:1–15

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 270:25872–25878

    Article  CAS  PubMed  Google Scholar 

  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 267:13943–13951

    CAS  PubMed  Google Scholar 

  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 266:20380–20389

    CAS  PubMed  Google Scholar 

  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 87:821–825

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 193:529–534

    Article  CAS  PubMed  Google Scholar 

  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):91–95

    Article  CAS  PubMed  Google Scholar 

  11. Lolli G, Pinna LA, Battistutta R (2012) Structural determinants of protein kinase CK2 regulation by autoinhibitory polymerization. ACS Chem Biol 7:1158–1163

    Article  CAS  PubMed  Google Scholar 

  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 3–75

    Google Scholar 

  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 20:5320–5331

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Niefind K, Raaf J, Issinger OG (2009) Protein kinase CK2: from structures to insights. Cell Mol Life Sci 66:1800–1816

    Article  CAS  PubMed  Google Scholar 

  15. Glover CVC (1998) On the physiological role of casein kinase II in Saccharomyces cerevisiae. Prog Nucleic Acid Res Mol Biol 59:95–133

    Article  CAS  PubMed  Google Scholar 

  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 273:5869–5877

    Article  CAS  PubMed  Google Scholar 

  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 23:908–915

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 28:131–139

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Xu X, Toselli PA, Russell LD, Seldin DC (1999) Globozoospermia in mice lacking the casein kinase II α′ catalytic subunit. Nat Genet 23:118–121

    Article  CAS  PubMed  Google Scholar 

  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 66:190–201

    Article  CAS  PubMed  Google Scholar 

  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 262:9136–9140

    CAS  PubMed  Google Scholar 

  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 1793:847–859

    Article  CAS  PubMed  Google Scholar 

  23. Meggio F, Pinna LA (2003) One-thousand-and-one substrates of protein kinase CK2? FASEB J 17:349–368

    Article  CAS  PubMed  Google Scholar 

  24. Litchfield DW, Dobrowolska G, Krebs EG (1994) Regulation of casein kinase II by growth factors: a reevaluation. Cell Mol Biol Res 40:373–381

    CAS  PubMed  Google Scholar 

  25. Hathaway GM, Traugh JA (1982) Casein kinases—multipotential protein kinases. Curr Top Cell Regul 21:101–127

    Article  CAS  PubMed  Google Scholar 

  26. Montenarh M (2010) Cellular regulators of protein kinase CK2. Cell Tissue Res 342:139–146

    Article  CAS  PubMed  Google Scholar 

  27. Montenarh M (2003) Protein kinase CK2: in search for its regulation. Adv Clin Exp Med 12:15–22

    Google Scholar 

  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 76–116

    Chapter  Google Scholar 

  29. Guerra B, Boldyreff B, Sarno S, Cesaro L, Issinger OG, Pinna LA (1999) CK2: A protein kinase in need of control. Pharmacol Ther 82:303–313

    Article  CAS  PubMed  Google Scholar 

  30. Faust M, Montenarh M (2000) Subcellular localization of protein kinase CK2: a key to its function? Cell Tissue Res 301:329–340

    Article  CAS  PubMed  Google Scholar 

  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 266:2362–2368

    CAS  PubMed  Google Scholar 

  32. Mestres P, Boldyreff B, Ebensperger C, Hameister H, Issinger O-G (1994) Expression of casein kinase 2 during mouse embryogenesis. Acta Anat 149:13–20

    Article  CAS  PubMed  Google Scholar 

  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 40:581–585

    CAS  PubMed  Google Scholar 

  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 587:1820–1828

    Article  Google Scholar 

  35. Ulloa L, Diaz-Nido J, Avila J (1993) Depletion of casein kinase II by antisense oligonucleotide prevents neuritogenesis in neuroblastoma cells. EMBO J 12:1633–1640

    PubMed Central  CAS  PubMed  Google Scholar 

  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 218:409–420

    Article  CAS  PubMed  Google Scholar 

  37. Singh TJ, Huang K (1985) Glycogen synthase (casein) kinase I: tissue distribution and subcellular localization. FEBS Lett 190:84–88

    Article  CAS  PubMed  Google Scholar 

  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 462:353–357

    Article  CAS  PubMed  Google Scholar 

  39. Nakajo S, Hagiwara T, Nakajo K, Nakamura Y (1986) Tissue distribution of casein kinases. Biochem Int 13:701–707

    CAS  PubMed  Google Scholar 

  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 55:1772–1783

    Article  CAS  PubMed  Google Scholar 

  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 202:141–147

    Article  CAS  PubMed  Google Scholar 

  42. Blanquet PR (2000) Casein kinase 2 as a potentially important enzyme in the nervous system. Prog Neurobiol 60:211–246

    Article  CAS  PubMed  Google Scholar 

  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 191:201–205

    Article  CAS  PubMed  Google Scholar 

  44. De Camilli P, Greengard P (1986) Synapsin I: a synaptic vesicle-associated neuronal phosphoprotein. Biochem Pharmacol 35:4349–4357

    Article  PubMed  Google Scholar 

  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 8:47–54

    Article  CAS  PubMed  Google Scholar 

  46. Iimoto DS, Masliah E, Deteresa R, Terry RD, Saitoh T (1990) Aberrant casein kinase II in Alzheimer’s disease. Brain Res 507:273–280

    Article  CAS  PubMed  Google Scholar 

  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 140:263–268

    PubMed Central  CAS  PubMed  Google Scholar 

  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 573:126–132

    Article  CAS  PubMed  Google Scholar 

  49. Jin LW, Saitoh T (1995) Changes in protein kinases in brain aging and Alzheimer’s disease. Implications for drug therapy. Drugs Aging 6:136–149

    Article  CAS  PubMed  Google Scholar 

  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 266:9–12

    Article  PubMed  Google Scholar 

  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 30:2737–2749

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Ahmed K, Ishida H (1971) Effect of testosterone on nuclear phosphoproteins of rat ventral prostate. Mol Pharmacol 7:323–327

    CAS  PubMed  Google Scholar 

  53. Ahmed K, Tawfic S (1994) Mechanism of intracellular regulation of protein kinase CK2: role of stimulus-mediated subnuclear association. Cell Mol Biol Res 40:539–545

    CAS  PubMed  Google Scholar 

  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 90:4426–4430

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Yu SH, Wang HM, Davis A, Ahmed K (2001) Consequences of CK2 signaling to the nuclear matrix. Mol Cell Biochem 227:67–71

    Article  CAS  PubMed  Google Scholar 

  56. Zhang S, Kim KH (1997) Protein kinase CK2 down-regulates glucose-activated expression of the acetyl-CoA carboxylase gene. Arch Biochem Biophys 338:227–232

    Article  CAS  PubMed  Google Scholar 

  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 84:8834–8838

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Sommercorn J, Krebs EG (1987) Induction of casein kinase II during differentiation of 3T3-L1 cells. J Biol Chem 262:3839–3843

    CAS  PubMed  Google Scholar 

  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 401:203–206

    Article  CAS  PubMed  Google Scholar 

  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 67:2481–2489

    Article  CAS  PubMed  Google Scholar 

  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 45:2786–2795

    Article  CAS  PubMed  Google Scholar 

  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 43:1809–1818

    CAS  PubMed  Google Scholar 

  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 147:2122–2129

    CAS  PubMed  Google Scholar 

  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 227:81–90

    Article  CAS  PubMed  Google Scholar 

  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 274:15–22

    Article  CAS  PubMed  Google Scholar 

  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 269:24615–24620

    CAS  PubMed  Google Scholar 

  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 24:11–16

    Article  CAS  PubMed  Google Scholar 

  68. Ahmad KA, Wang G, Unger G, Slaton J, Ahmed K (2008) Protein kinase CK2- A key suppressor of apoptosis. Adv Enzyme Regul 48:179–187

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 319–343

    Chapter  Google Scholar 

  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 26:1567–1575

    Article  CAS  PubMed  Google Scholar 

  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 37:115–132

    CAS  PubMed  Google Scholar 

  72. Faust M, Schuster N, Montenarh M (1999) Specific binding of protein kinase CK2 catalytic subunits to tubulin. FEBS Lett 462:51–56

    Article  CAS  PubMed  Google Scholar 

  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 130:167–178

    CAS  PubMed  Google Scholar 

  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 36:1139–1145

    Article  CAS  PubMed  Google Scholar 

  75. Efrat S (1999) Genetically engineered pancreatic beta-cell lines for cell therapy of diabetes. Ann N Y Acad Sci 875:286–293

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Gebäude 44, 66424, Homburg, Germany

    Sabrina Welker, Christina Servas, Meng Rui, Claudia Götz & Mathias Montenarh

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  1. Sabrina Welker
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  2. Christina Servas
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  3. Meng Rui
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  4. Claudia Götz
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  5. Mathias Montenarh
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Correspondence to Mathias Montenarh .

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Editors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Minnesota Medical School and Minneapolis VA Health Care System, Minneapolis, Minnesota, USA

    Khalil Ahmed

  2. Dept of Biochemistry & Molecular Biology, University of Southern Denmark, Odense, Denmark

    Olaf-Georg Issinger

  3. Department of Molecular Biology, The John Paul II Catholic U. of Lublin Institute of Biotechnology, Lublin, Poland

    Ryszard Szyszka

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Welker, S., Servas, C., Rui, M., Götz, C., Montenarh, M. (2015). Tissue-Specific Functions and Regulation of Protein Kinase CK2. In: Ahmed, K., Issinger, OG., Szyszka, R. (eds) Protein Kinase CK2 Cellular Function in Normal and Disease States. Advances in Biochemistry in Health and Disease, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-14544-0_7

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