Advances in Clinical and Experimental Medicine

Adv Clin Exp Med
Impact Factor (IF) – 1.227
Index Copernicus (ICV 2018) – 157.72
MNiSW – 40
Average rejection rate – 84.38%
ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download PDF

Advances in Clinical and Experimental Medicine

2014, vol. 23, nr 2, March-April, p. 153–158

Publication type: editorial article

Language: English

Protein Kinase CK2 and Angiogenesis

Mathias Montenarh1,

1 Medical Biochemistry and Molecular Biology, Saarland University, Homburg

Abstract

CK2 is an ubiquitously expressed protein kinase, which is composed of two catalytic a and a’- and two noncatalytic b-subunits. CK2 protein levels and kinase activity is elevated in rapidly proliferating cells including cancer cells. There is increasing evidence that CK2 also plays an essential role in angiogenesis, either by interaction or phosphorylation of growth factors or by phosphorylation or binding to proteins in signalling cascades, which are implicated in angiogenesis. Over the last ten years a great number of inhibitors for CK2 were detected, two of them are now in clinical phase II trials for the treatment of cancer patients. Some of these inhibitors were also found to be active in the inhibition of angiogenesis. Thus, CK2 inhibitors probably together with inhibitors of other signalling molecules involved in angiogenesis might be powerful tools for the treatment of cancer and cancer connected angiogenesis.

Key words

protein kinase CK2, cancer, angiogenesis, retina, neovascularization.

References (72)

  1. Burnett G, Kennedy EP: The enzymatic phosphorylation of proteins. J Biol Chem 1954, 211, 969–980.
  2. Lozeman FJ, Litchfield DW, Piening C, Takio K, Walsh KA, Krebs EG: Isolation and characterization of human clones encoding the a and the a’ subunits of casein kinase II. Biochemistry 1990, 29, 8436–8447.
  3. Glover CVC: On the physiological role of casein kinase II in Saccharomyces cerevisiae. Prog Nucleic Acid Res Mol Biol 1998, 59, 95–133.
  4. Rethinaswamy A, Birnbaum MJ, Glover CVC: 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 1998, 273, 5869– 5877.
  5. Buchou T, Vernet M, Blond O, Jensen HH, Pointu H, Olsen BB, Cochet C, Issinger OG, Boldyreff B: Disruption of the regulatory b subunit of protein kinase CK2 in mice leads to a cell-autonomous defect and early embryonic lethality. Mol Cell Biol 2003, 23, 908–915.
  6. Lou DY, Dominguez I, Toselli P, Landesman-Bollag E, O’Brien C, Seldin DC: The alpha catalytic subunit of protein kinase CK2 is required for mouse embryonic development. Mol Cell Biol 2008, 28, 131–139.
  7. Xu X, Toselli PA, Russell LD, Seldin DC: Globozoospermia in mice lacking the casein kinase II a’ catalytic subunit. Nature Genet 1999, 23, 118–121.
  8. Escalier D, Silvius D, Xu X: Spermatogenesis of mice lacking CK2a’: Failure of germ cell survival and characteristic modifications of the spermatid nucleus. Mol Reprod Dev 2003, 66, 190–201.
  9. Salvi M, Sarno S, Cesaro L, Nakamura H, Pinna LA: Extraordinary pleiotropy of protein kinase CK2 revealed by weblogo phosphoproteome analysis. Biochim Biophys Acta 2009, 1793, 847–859.
  10. Faust M, Montenarh M: Subcellular localization of protein kinase CK2: A key to its function? Cell Tissue Res 2000, 301, 329–340.
  11. Montenarh M: Cellular regulators of protein kinase CK2. Cell Tissue Res 2010, 342, 139–146.
  12. Valero E, De Bonis S, Filhol O, Wade RH, Langowski J, Chambaz EM, Cochet C: Quaternary structure of casein kinase 2. Characterization of multiple oligomeric states and relation with catalytic activity. J Biol Chem 1995, 270, 8345–8352.
  13. Lolli G, Pinna LA, Battistutta R: Structural determinants of protein kinase CK2 regulation by autoinhibitory polymerization. ACS Chem Biol 2012, 7, 1158–1163.
  14. Landesman-Bollag E, Romieu-Mourez R, Song DH, Sonenshein GE, Cardiff RD, Seldin DC: Protein kinase CK2 in mammary gland tumorigenesis. Oncogene 2001, 20, 3247–3257.
  15. Laramas M, Pasquier D, Filhol O, Ringeisen F, Descotes JL, Cochet C: Nuclear localization of protein kinase CK2 catalytic subunit (CK2alpha) is associated with poor prognostic factors in human prostate cancer. Eur J Cancer 2007, 43, 928–934.
  16. Stalter G, Siemer S, Becht E, Ziegler M, Remberger K, Issinger O-G: Asymmetric expression of protein kinase CK2 in human kidney tumors. Biochem Biophys Res Commun 1994, 202, 141–147.
  17. Lin KY, Tai C, Hsu JC, Li CF, Fang CL, Lai HC, Hseu YC, Lin YF, Uen YH: Overexpression of Nuclear Protein Kinase CK2 alpha Catalytic Subunit (CK2alpha) as a Poor Prognosticator in Human Colorectal Cancer. PLoS ONE 2011, 6, e17193 .
  18. Faust RA, Gapany M, Tristani P, Davis A, Adams GL, Ahmed K: Elevated protein kinase CK2 activity in chromatin of head and neck tumors: Association with malignant transformation. Cancer Lett 1996, 101, 31–35.
  19. Daya-Makin M, Sanghera JS, Mogentale TL, Lipp M, Parchomchuk J, Hogg JC, Pelech SL: Activation of a tumor-associated protein kinase (p40TAK) and casein kinase 2 in human squamous cell carcinomas and adenocarcinomas of the lung. Cancer Res 1994, 54, 2262–2268.
  20. Ahmad KA, Wang G, Unger G, Slaton J, Ahmed K: Protein kinase CK2- A key suppressor of apoptosis. Adv Enzyme Regul 2008, 48, 179–187.
  21. Slaton JW, Unger GM, Sloper DT, Davis AT, Ahmed K: Induction of apoptosis by antisense CK2 in human prostate cancer xenograft model. Cell Growth Differ 2004, 2, 712–721.
  22. Wang G, Unger G, Ahmad KA, Slaton JW, Ahmed K: Downregulation of CK2 induces apoptosis in cancer cells-a potential approach to cancer therapy. Mol Cell Biochem 2005, 274, 77–84.
  23. Mendrysa SM, Perry ME: The p53 tumor suppressor protein does not regulate expression of its own inhibitor, MDM2, except under conditions of stress. Mol Cell Biol 2000, 20, 2023–2030.
  24. Schneider HR, Reichert GH, Issinger OG: Enhanced casein kinase II activity during mouse embryogenesis. Identification of a 110-kDa phosphoprotein as the major phosphorylation product in mouse embryos and Krebs II mouse ascites tumor cells. Eur J Biochem 1986, 161, 733–738.
  25. Diaz-Nido J, Mizuno K, Nawa H, Marshak DR: Regulation of protein kinase Ck2 isoform expression during rat brain development. Cell Mol Biol Res 1994, 40, 581–585.
  26. Huillard E, Ziercher L, Blond O, Wong M, Deloulme JC, Souchelnytskyi S, Baudier J, Cochet C, Buchou T: Disruption of CK2beta in embryonic neural stem cells compromises proliferation and oligodendrogenesis in the mouse telencephalon. Mol Cell Biol 2010, 30, 2737–2749.
  27. Dominguez I, Degano IR, Chea K, Cha J, Toselli P, Seldin DC: CK2alpha is essential for embryonic morphogenesis. Mol Cell Biochem 2011, 356, 209–216.
  28. Wilhelm N, Kostelnik K, Götz C, Montenarh M: Protein kinase CK2 is implicated in early steps of the differentiation of preadipocytes into adipocytes. Mol Cell Biochem 2012, 365, 37–45.
  29. Sommercorn J, Krebs EG: Induction of casein kinase II during differentiation of 3T3-L1 cells. J Biol Chem 1987, 262, 3839–3843.
  30. Song C, Li Z, Erbe AK, Savic A, Dovat S: Regulation of Ikaros function by casein kinase 2 and protein phosphatase 1. World J Biol Chem 2011, 2, 126–131.
  31. Dovat S, Song C, Payne KJ, Li Z: Ikaros, CK2 kinase, and the road to leukemia. Mol Cell Biochem 2011, 356, 201–207.
  32. Ahmed K, Gerber DA, Cochet C: Joining the cell survival squad: an emerging role for protein kinase CK2. Trends Cell Biol 2002, 12, 226–230.
  33. Song DH, Dominguez I, Mizuno J, Kaut M, Mohr SC, Seldin DC: CK2 phosphorylation of the armadillo repeat region of b-catenin potentiates Wnt signaling. J Biol Chem 2003, 278, 24018–24025.
  34. Song DH, Sussman DJ, Seldin DC: Endogenous protein kinase CK2 participates in Wnt signaling in mammary epithelial cells. J Biol Chem 2000, 275, 23790–23797.
  35. Zhang S, Wang Y, Mao JH, Hsieh D, Kim IJ, Hu LM, Xu Z, Long H, Jablons DM, You L: Inhibition of CK2alpha Down-Regulates Hedgehog/Gli Signaling Leading to a Reduction of a Stem-Like Side Population in Human Lung Cancer Cells. PLoS ONE 2012, 7, e38996.
  36. Barata JT: The impact of PTEN regulation by CK2 on PI3K-dependent signaling and leukemia cell survival. Adv Enzyme Regul 2010, 51, 37-49.
  37. Mottet D, Ruys SP, Demazy C, Raes M, Michiels C: Role for casein kinase 2 in the regulation of HIF-1 activity. Int J Cancer 2005, 117, 764–774.
  38. Al-Quobaili F, Montenarh M: CK2 and the regulation of the carbohydrate metabolism. Metabolism 2012, 61, 1512–1517.
  39. Meng R, Al-Quobaili F, Müller I, Götz C, Thiel G, Montenarh M: CK2 phosphorylation of Pdx-1 regulates its transcription factor activity. Cell Mol Life Sci 2010, 67, 2481–2489.
  40. Meng R, Götz C, Montenarh M: The role of protein kinase CK2 in the regulation of the insulin production of pancreatic islets. Biochem Biophys Res Commun 2010, 401, 203–206.
  41. Welker S, Götz C, Servas C, Laschke MW, Menger MD, Montenarh M: Glucose regulates protein kinase CK2 in pancreatic ß-cells and its interaction with PDX-1. Int J Biochem Cell Biol 2013, 384, 71–82.
  42. Feng D, Welker S, Korbel C, Rudzitis-Auth J, Menger MD, Montenarh M, Laschke MW: Protein kinase CK2 is a regulator of angiogenesis in endometriotic lesions. Angiogenesis 2012, 15, 243–252.
  43. Noy P, Sawasdichai A, Jayaraman PS, Gaston K: Protein kinase CK2 inactivates PRH/Hhex using multiple mechanisms to de-repress VEGF-signalling genes and promote cell survival. Nucleic Acids Res 2012, 40, 9008–9020.
  44. Afonyushkin T, Oskolkova OV, Binder BR, Bochkov VN: Involvement of CK2 in activation of electrophilic genes in endothelial cells by oxidized phospholipids. J Lipid Res 2011, 52, 98–103.
  45. Pollreisz A, Afonyushkin T, Oskolkova OV, Gruber F, Bochkov VN, Schmidt-Erfurth U: Retinal pigment epithelium cells produce VEGF in response to oxidized phospholipids through mechanisms involving ATF4 and protein kinase CK2. Exp Eye Res 2013, 116C, 177–184.
  46. Bonnet H, Filhol O, Truchet I, Brethenou P, Cochet C, Amalric F, Bouche G: Fibroblast growth factor-2 binds to the regulatory b subunit of CK2 and directly stimulates CK2 activity toward nucleolin. J Biol Chem 1996, 271, 24781–24787.
  47. Skjerpen CS, Nilsen T, Wesche J, Olsnes S: Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity. EMBO Journal 2002, 21, 4058–4069.
  48. Maik-Rachline G, Shaltiel S, Seger R: Extracellular phosphorylation converts pigment epithelium-derived factor from a neurotrophic to an antiangiogenic factor. Blood 2005, 105, 670–678.
  49. Maik-Rachline G, Seger R: Variable phosphorylation states of pigment-epithelium-derived factor differentially regulate its function. Blood 2006, 107, 2745–2752.
  50. Garat CV, Crossno JT, Jr., Sullivan TM, Reusch JE, Klemm DJ: Thiazolidinediones prevent PDGF-BB-induced CREB depletion in pulmonary artery smooth muscle cells by preventing upregulation of casein kinase 2 alpha’ catalytic subunit. J Cardiovasc Pharmacol 2010, 55, 469–480.
  51. Massague J: TGF-beta signal transduction. Annu Rev Biochem 1998, 67, 753–791.
  52. Urness LD, Sorensen LK, Li DY: Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Nat Genet 2000, 26, 328–331.
  53. Lee NY, Haney JC, Sogani J, Blobe GC: Casein kinase 2{beta} as a novel enhancer of activin-like receptor-1 signaling. FASEB J 2009, 3712–3721.
  54. Lieberman SL, Ruderman JV: CK2b, which inhibits Mos function, binds to a discrete domain in the N-terminus of Mos. Dev Biol 2004, 268, 271–279.
  55. Hagemann C, Kalmes A, Wixler V, Wixler L, Schuster T, Rapp UR: The regulatory subunit of protein kinase CK2 is a specific A-Raf activator. FEBS Lett 1997, 403, 200–202.
  56. Guerra B, Issinger OG, Wang JYJ: Modulation of human checkpoint kinase Chk1 by the regulatory b-subunit of protein kinase CK2. Oncogene 2003, 22, 4933–4942.
  57. Luz S, Kongsuphol P, Mendes AI, Romeiras F, Sousa M, Schreiber R, Matos P, Jordan P, Mehta A, Amaral MD, Kunzelmann K, Farinha CM: Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity. Mol Cell Biol 2011, 31, 4392–4404.
  58. DiMaira G, Salvi M, Arrigoni G, Marin O, Sarno S, Brustolon F, Pinna LA, Ruzzene M: Protein kinase CK2 phosphorylates and upregulates Akt/PKB. Cell Death Differ 2005, 12, 668–677.
  59. Ponce DP, Maturana JL, Cabello P, Yefi R, Niechi I, Silva E, Armisen R, Galindo M, Antonelli M, Tapia JC: Phosphorylation of AKT/PKB by CK2 is necessary for the AKT-dependent up-regulation of beta-catenin transcriptional activity. J Cell Physiol 2011, 226, 1953–1959.
  60. Guerra B: Protein kinase CK2 subunits are positive regulators of AKT kinase. Int J Oncol 2006, 28, 685–693.
  61. Ponce DP, Yefi R, Cabello P, Maturana JL, Niechi I, Silva E, Galindo M, Antonelli M, Marcelain K, Armisen R, Tapia JC: CK2 functionally interacts with AKT/PKB to promote the beta-catenin-dependent expression of survivin and enhance cell survival. Mol Cell Biochem 2011, 356, 127–132.
  62. Isaeva AR, Mitev VI: CK2 is acting upstream of MEK3/6 as a part of the signal control of ERK1/2 and p38 MAPK during keratinocytes autocrine differentiation. Z Naturforsch C 2011, 66, 83–86.
  63. Olsen BB, Svenstrup TH, Guerra B: Downregulation of protein kinase CK2 induces autophagic cell death through modulation of the mTOR and MAPK signaling pathways in human glioblastoma cells. Int J Oncol 2012, 41, 1967–1976.
  64. Hubert A, Paris S, Piret JP, Ninane N, Raes M, Michiels C: Casein kinase 2 inhibition decreases hypoxia-inducible factor-1 activity under hypoxia through elevated p53 protein level. J Cell Sci 2006, 119, 3351–3362.
  65. Ampofo E, Kietzmann T, Zimmer A, Jakupovic M, Montenarh M, Götz C: Phosphorylation of the von HippelLindau protein (VHL) by protein kinase CK2 reduces its protein stability and affects p53 and HIF-1a mediated transcription. Int J Biochem Cell Biol 2010, 42, 1729–1735.
  66. Ljubimov AV, Caballero S, Aoki AM, Pinna LA, Grant MB, Castellon R: Involvement of protein kinase CK2 in angiogenesis and retinal neovascularization. Invest Ophthalmol Vis Sci 2004, 45, 4583–4591.
  67. Kramerov AA, Saghizadeh M, Pan H, Kabosova A, Montenarh M, Ahmed K, Penn JS, Chan CK, Hinton DR, Grant MB, Ljubimov AV: Expression of protein kinase CK2 in astroglial cells of normal and neovascularized retina. Am J Pathol 2006, 168, 1722–1736.
  68. Kramerov AA, Saghizadeh M, Caballero S, Shaw LC, Li Calzi S., Bretner M, Montenarh M, Pinna LA, Grant MB, Ljubimov AV: Inhibition of protein kinase CK2 suppresses angiogenesis and hematopoietic stem cell recruitment to retinal neovascularization sites. Mol Cell Biochem 2008, 316, 177–183.
  69. Kramerov AA, Golub AG, Bdzhola VG, Yarmoluk SM, Ahmed K, Bretner M, Ljubimov AV: Treatment of cultured human astrocytes and vascular endothelial cells with protein kinase CK2 inhibitors induces early changes in cell shape and cytoskeleton. Mol Cell Biochem 2010, 349, 125–137.
  70. Kramerov AA, Ahmed K, Ljubimov AV: Cell rounding in cultured human astrocytes and vascular endothelial cells upon inhibition of CK2 is mediated by actomyosin cytoskeleton alterations. J Cell Biochem 2012, 113, 2948–2956.
  71. Farina HG, Benavent AF, Perera Y, Rodriguez A, Perea SE, Castro BA, Gomez R, Alonso DF, Gomez DE: CIGB-300, a proapoptotic peptide, inhibits angiogenesis in vitro and in vivo. Exp Cell Res 2011, 317, 1677–1688.
  72. Jo N, Mailhos C, Ju M, Cheung E, Bradley J, Nishijima K, Robinson GS, Adamis AP, Shima DT: Inhibition of platelet-derived growth factor B signaling enhances the efficacy of anti-vascular endothelial growth factor therapy in multiple models of ocular neovascularization. Am J Pathol 2006, 168, 2036–2053.