Abstract
Protein kinase CK2 represents a small family of highly conserved protein kinases involved in a complex series of cellular events. Furthermore, CK2 has been localised to many discrete cellular sites and has an extensive and diverse array of substrates and interaction partners in cells. Despite considerable investigation, the precise mechanism(s) of regulation of CK2 in cells remains poorly understood. In consideration of the prospect that cells contain many distinct sub-populations of CK2 that are distinguished on the basis of localisation and/or interactions with other cellular components, one possibility is that there may be differential regulation of specific sub-populations of CK2. With this in mind, some of the individual sub-populations of CK2 may be regulated through particular protein–protein interactions that may play a role in recruiting CK2 into the vicinity of its substrates and/or modulating its ability to phosphorylate specific cellular targets. In this respect, here we examine two CK2-interacting proteins, namely Pin1 and CKIP-1 that have been shown to participate in the modulation of CK2 specificity or the subcellular localisation of CK2, respectively. One aspect of this work has been focused on the prospect that Pin1 interacts with CK2 in response to UV stimulation in a manner analogous to the phosphorylation-dependent interactions of CK2 that occur following the mitotic phosphorylation of CK2. A second aspect of this work involves an examination of the structural basis for interactions between CK2 and CKIP-1 with emphasis on a putative HIKE domain in CK2.
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Litchfield DW, Luscher B: Casein kinase II in signal transduction and cell cycle regulation. Mol Cell Biochem 127–128: 187–199, 1993
Allende JE, Allende CC: Protein kinases. 4. Protein kinase CK2: an enzyme with multiple substrates and a puzzling regulation. FASEB J 9: 313–323, 1995
Guerra B, Boldyreff B, Sarno S, Cesaro L, Issinger OG, Pinna LA: CK2: a protein kinase in need of control. Pharmacol Ther 82: 303–313, 1999
Guo C, Yu S, Davis AT, Wang H, Green JE, Ahmed K: a potential role of nuclear matrix-associated protein kinase CK2 in protection against drug-induced apoptosis in cancer cells. J Biol Chem 276: 5992–5999, 2001
Tawfic S, Yu S, Wang H, Faust R, Davis A, Ahmed K: Protein kinase CK2 signal in neoplasia. Histol Histopathol 16: 573–582, 2001
Ahmed K, Davis AT, Wang H, Faust RA, Yu S, Tawfic S: Significance of protein kinase CK2 nuclear signaling in neoplasia. J Cell Biochem 35: 130–135, 2000
Ahmed K, Gerber DA, Cochet C: Joining the cell survival squad: an emerging role for protein kinase CK2. Trends Cell Biol 12: 226–230, 2002
Ghavidel A, Schultz MC: TATA binding protein-associated CK2 transduces DNA damage signals to the RNA polymerase III transcriptional machinery. Cell 106: 575–584, 2001
Issinger OG: Casein kinases: pleiotropic mediators of cellular regulation. Pharmacol Ther 59: 1–30, 1993
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 54: 2262–2268, 1994
Stalter G, Siemer S, Becht E, Ziegler M, Remberger K, Issinger OG: Asymmetric expression of protein kinase CK2 subunits in human kidney tumors. Biochem Biophys Res Commun 202: 141–147, 1994
Yenice S, Davis AT, Goueli SA, Akdas A, Limas C, Ahmed K: Nuclear casein kinase 2 (CK-2) activity in human normal, benign hyperplastic, and cancerous prostate. Prostate 24: 11–16, 1994
Pinna LA: A historical view of protein kinase CK2. Cell Mol Biol Res 40: 383–390, 1994
Pinna LA: Protein kinase CK2. Int J Biochem Cell Biol 29: 551–554, 1997
Pinna LA: Protein kinase CK2: a challenge to canons. J Cell Sci 115: 3873–3878, 2002
Meggio F, Pinna LA: One-thousand-and-one substrates of protein kinase CK2? FASEB J 17: 349–368, 2003
Litchfield DW: Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J 369: 1–15, 2003
Berberich SJ, Cole MD: Casein kinase II inhibits the DNA-binding activity of Max homodimers but not Myc/Max heterodimers. Genes Dev 6: 166–176, 1992
Cardenas ME, Dang Q, Glover CV, Gasser SM: Casein kinase II phosphorylates the eukaryote-specific C-terminal domain of topoisomerase II in vivo. Embo J 11: 1785–1796, 1992
Lin A, Frost J, Deng T, Smeal T, Al-Alawi N, Kikkawa U, Hunter T, Brenner D, Karin M: Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity. Cell 70: 777–789, 1992
Milne DM, Palmer RH, Meek DW: Mutation of the casein kinase II phosphorylation site abolishes the anti-proliferative activity of p53. Nucleic Acids Res 20: 5565–5570, 1992
Luscher B, Kuenzel EA, Krebs EG, Eisenman RN: Myc oncoproteins are phosphorylated by casein kinase II. Embo J 8: 1111–1119, 1989
Boldyreff B, Issinger OG: A-Raf kinase is a new interacting partner of protein kinase CK2 beta subunit. FEBS Lett 403: 197–199, 1997
Heriche JK, Lebrin F, Rabilloud T, Leroy D, Chambaz EM, Goldberg Y: Regulation of protein phosphatase 2A by direct interaction with casein kinase 2alpha. Science 276: 952–955, 1997
Ulloa L, Diaz-Nido J, Avila J: Depletion of casein kinase II by antisense oligonucleotide prevents neuritogenesis in neuroblastoma cells. Embo J 12: 1633–1640, 1993
Wei T, Tao M: Human erythrocyte casein kinase II: characterization and phosphorylation of membrane cytoskeletal proteins. Arch Biochem Biophys 307: 206–216, 1993
Sargiacomo M, Scherer PE, Tang ZL, Casanova JE, Lisanti MP: In vitro phosphorylation of caveolin-rich membrane domains: identification of an associated serine kinase activity as a casein kinase II-like enzyme. Oncogene 9: 2589–2595, 1994
Robinson PJ, Sontag JM, Liu JP, Fykse EM, Slaughter C, McMahon H, Sudhof TC: Dynamin GTPase regulated by protein kinase C phosphorylation in nerve terminals. Nature 365: 163–166, 1993
Olsten MEK, Litchfield DW: Order or chaos? An evaluation of the regulation of protein kinase CK2. Biochem Cell Biol 2004
Keller DM, Lu H: p53 Serine 392 phosphorylation increases after UV through induction of the assembly of the CK2.hSPT16.SSRP1 complex. J Biol Chem 277: 50206–50213, 2002
Keller DM, Zeng X, Wang Y, Zhang QH, Kapoor M, Shu H, Goodman R, Lozano G, Zhao Y, Lu H: A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. Mol Cell 7: 283–292, 2001
Messenger MM, Saulnier RB, Gilchrist AD, Diamond P, Gorbsky GJ, Litchfield DW: Interactions between protein kinase CK2 and Pin1. Evidence for phosphorylation-dependent interactions. J Biol Chem 277: 23054–23064, 2002
Bosc DG, Graham KC, Saulnier RB, Zhang C, Prober D, Gietz RD, Litchfield DW: Identification and characterization of CKIP-1, a novel pleckstrin homology domain-containing protein that interacts with protein kinase CK2. J Biol Chem 275: 14295–14306, 2000
Olsten ME, Canton DA, Zhang C, Walton PA, Litchfield DW: The Pleckstrin homology domain of CK2 interacting protein-1 is required for interactions and recruitment of protein kinase CK2 to the plasma membrane. J Biol Chem 279: 42114–42127, 2004
Faust M, Gunther J, Morgenstern E, Montenarh M, Gotz C: Specific localization of the catalytic subunits of protein kinase CK2 at the centrosomes. Cell Mol Life Sci 59: 2155–2164, 2002
Faust M, Schuster N, Montenarh M: Specific binding of protein kinase CK2 catalytic subunits to tubulin. FEBS Lett 462: 51–56, 1999
Alberti S: A phosphoinositide-binding sequence is shared by PH domain target molecules – a model for the binding of PH domains to proteins. Proteins 31: 1–9, 1998
Alberti S: HIKE, a candidate protein binding site for PH domains, is a major regulatory region of Gbeta proteins. Proteins 35: 360–363, 1999
Gietz RD, Graham KC, Litchfield DW: Interactions between the subunits of casein kinase II. J Biol Chem 270: 13017–13021, 1995
Vilk G, Saulnier RB, St Pierre R, Litchfield DW: Inducible expression of protein kinase CK2 in mammalian cells. Evidence for functional specialization of CK2 isoforms. J Biol Chem 274: 14406–14414, 1999
Litchfield DW, Dobrowolska G, Krebs EG: Regulation of casein kinase II by growth factors: a reevaluation. Cell Mol Biol Res 40: 373–381, 1994
Filhol O, Nueda A, Martel V, Gerber-Scokaert D, Benitez MJ, Souchier C, Saoudi Y, Cochet C: Live-cell fluorescence imaging reveals the dynamics of protein kinase CK2 individual subunits. Mol Cell Biol 23: 975–987, 2003
Martel V, Filhol O, Nueda A, Cochet C: Dynamic localization/association of protein kinase CK2 subunits in living cells: a role in its cellular regulation? Ann N Y Acad Sci 973: 272–277, 2002
Leroy D, Filhol O, Delcros JG, Pares S, Chambaz EM, Cochet C: Chemical features of the protein kinase CK2 polyamine binding site. Biochemistry 36: 1242–1250, 1997
Leroy D, Heriche JK, Filhol O, Chambaz EM, Cochet C: Binding of polyamines to an autonomous domain of the regulatory subunit of protein kinase CK2 induces a conformational change in the holoenzyme. A proposed role for the kinase stimulation. J Biol Chem 272: 20820–20827, 1997
Lu KP, Hanes SD, Hunter T: A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature 380: 544–547, 1996
Lu KP, Liou YC, Vincent I: Proline-directed phosphorylation and isomerization in mitotic regulation and in Alzheimer’s disease. Bioessays 25: 174–181, 2003
Lu KP: Phosphorylation-dependent prolyl isomerization: a novel cell cycle regulatory mechanism. Prog Cell Cycle Res 4: 83–96, 2000
Shen M, Stukenberg PT, Kirschner MW, Lu KP: The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteins. Genes Dev 12: 706–720, 1998
Yaffe MB, Schutkowski M, Shen M, Zhou XZ, Stukenberg PT, Rahfeld JU, Xu J, Kuang J, Kirschner MW, Fischer G, Cantley LC, Lu KP: Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism. Science 278: 1957–1960, 1997
Stukenberg PT, Kirschner MW: Pin1 acts catalytically to promote a conformational change in Cdc25. Mol Cell 7: 1071–1083, 2001
Lu KP, Liou YC, Zhou XZ: Pinning down proline-directed phosphorylation signaling. Trends Cell Biol 12: 164–172, 2002
Winkler KE, Swenson KI, Kornbluth S, Means AR: Requirement of the prolyl isomerase Pin1 for the replication checkpoint. Science 287: 1644–1647, 2000
Huang HK, Forsburg SL, John UP, O’Connell MJ, Hunter T: Isolation and characterization of the Pin1/Ess1p homologue in Schizosaccharomyces pombe. J Cell Sci 114: 3779–3788, 2001
Mantovani F, Gostissa M, Collavin L, Del Sal G: KeePin’ the p53 family in good shape. Cell Cycle 3: 905–911, 2004
Zheng H, You H, Zhou XZ, Murray SA, Uchida T, Wulf G, Gu L, Tang X, Lu KP, Xiao ZX: The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature 419: 849–853, 2002
Litchfield DW, Luscher B, Lozeman FJ, Eisenman RN, Krebs EG: Phosphorylation of casein kinase II by p34cdc2 in vitro and at mitosis. J Biol Chem 267: 13943–13951, 1992
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, 1995
Escargueil AE, Plisov SY, Filhol O, Cochet C, Larsen AK: Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase CK2 creates the MPM-2 phosphoepitope on Ser-1469. J Biol Chem 275: 34710–34718, 2000
Daum JR, Gorbsky GJ: Casein kinase II catalyzes a mitotic phosphorylation on threonine 1342 of human DNA topoisomerase IIalpha, which is recognized by the 3F3/2 phosphoepitope antibody. J Biol Chem 273: 30622–30629, 1998
Kapoor M, Lozano G: Functional activation of p53 via phosphorylation following DNA damage by UV but not gamma radiation. Proc Natl Acad Sci USA 95: 2834–2837, 1998
Meek DW, Campbell LE, Jardine LJ, Knippschild U, McKendrick L, Milne DM: Multi-site phosphorylation of p53 by protein kinases inducible by p53 and DNA damage. Biochem Soc Trans 25: 416–419, 1997
Wahl GM, Carr AM: The evolution of diverse biological responses to DNA damage: insights from yeast and p53. Nat Cell Biol 3: E277–E286, 2001
Niefind K, Guerra B, Ermakowa I, Issinger OG: Crystal structure of human protein kinase CK2: insights into basic properties of the CK2 holoenzyme. Embo J 20: 5320–5331, 2001
Colledge M, Scott JD: AKAPs: from structure to function. Trends Cell Biol 9: 216–221, 1999
Diviani D, Scott JD: AKAP signaling complexes at the cytoskeleton. J Cell Sci 114: 1431–1437, 2001
Pawson T, Scott JD: Signaling through scaffold, anchoring, and adaptor proteins. Science 278: 2075–2080, 1997
Smith FD, Scott JD: Signaling complexes: junctions on the intracellular information super highway. Curr Biol 12: R32–R40, 2002
Yu S, Davis AT, Guo C, Green JE, Ahmed K: Differential targeting of protein kinase CK2 to the nuclear matrix upon transient overexpression of its subunits. J Cell Biochem 74: 127–134, 1999
Guo C, Yu S, Davis AT, Ahmed K: Nuclear matrix targeting of the protein kinase CK2 signal as a common downstream response to androgen or growth factor stimulation of prostate cancer cells. Cancer Res 59: 1146–1151, 1999
Zhang P, Davis AT, Ahmed K: Mechanism of protein kinase CK2 association with nuclear matrix: role of disulfide bond formation. J Cell Biochem 69: 211–220, 1998
Ahmed K: Nuclear matrix and protein kinase CK2 signaling. Crit Rev Eukaryot Gene Expr 9: 329–336, 1999
McKendrick L, Milne D, Meek D: Protein kinase CK2-dependent regulation of p53 function: evidence that the phosphorylation status of the serine 386 (CK2) site of p53 is constitutive and stable. Mol Cell Biochem 191: 187–199, 1999
Krek W, Maridor G, Nigg EA: Casein kinase II is a predominantly nuclear enzyme. J Cell Biol 116: 43–55, 1992
Gerber DA, Souquere-Besse S, Puvion F, Dubois MF, Bensaude O, Cochet C: Heat-induced relocalization of protein kinase CK2. Implication of CK2 in the context of cellular stress. J Biol Chem 275: 23919–23926, 2000
Bosc DG, Luscher B, Litchfield DW: Expression and regulation of protein kinase CK2 during the cell cycle. Mol Cell Biochem 191: 213–222, 1999
Zhang C, Vilk G, Canton DA, Litchfield DW: Phosphorylation regulates the stability of the regulatory CK2beta subunit. Oncogene 21: 3754–3764, 2002
Meggio F, Boldyreff B, Marin O, Pinna LA, Issinger OG: Role of the beta subunit of casein kinase-2 on the stability and specificity of the recombinant reconstituted holoenzyme. Eur J Biochem 204: 293–297, 1992
Tuazon PT, Traugh JA: Casein kinase I and II – multipotential serine protein kinases: structure, function, and regulation. Adv Second Messenger Phosphoprotein Res 23: 123–164, 1991
Shore LJ, Soler AP, Gilmour SK: Ornithine decarboxylase expression leads to translocation and activation of protein kinase CK2 in vivo. J Biol Chem 272: 12536–12543, 1997
Meggio F, Brunati AM, Pinna LA: Polycation-dependent, Ca2+-antagonized phosphorylation of calmodulin by casein kinase-2 and a spleen tyrosine protein kinase. FEBS Lett 215: 241–246, 1987
Benaim G, Villalobo A: Phosphorylation of calmodulin. Functional implications. Eur J Biochem 269: 3619–3631, 2002
Marin O, Meggio F, Pinna LA: Structural features underlying the unusual mode of calmodulin phosphorylation by protein kinase CK2: a study with synthetic calmodulin fragments. Biochem Biophys Res Commun 256: 442–446, 1999
Graham KC, Litchfield DW: The regulatory beta subunit of protein kinase CK2 mediates formation of tetrameric CK2 complexes. J Biol Chem 275: 5003–5010, 2000
Boldyreff B, Mietens U, Issinger OG: Structure of protein kinase CK2: dimerization of the human beta-subunit. FEBS Lett 379: 153–156, 1996
Luscher B, Litchfield DW: Biosynthesis of casein kinase II in lymphoid cell lines. Eur J Biochem 220: 521–526, 1994
Litchfield DW, Lozeman FJ, Cicirelli MF, Harrylock M, Ericsson LH, Piening CJ, Krebs EG: 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, 1991
Meggio F, Boldyreff B, Marin O, Issinger OG, Pinna LA: Phosphorylation and activation of protein kinase CK2 by p34cdc2 are independent events. Eur J Biochem 230: 1025–1031, 1995
Boldyreff B, Meggio F, Pinna LA, Issinger OG: Reconstitution of normal and hyperactivated forms of casein kinase-2 by variably mutated beta-subunits. Biochemistry 32: 12672–12677, 1993
Sarno S, Marin O, Meggio F, Pinna LA: Polyamines as negative regulators of casein kinase-2: the phosphorylation of calmodulin triggered by polylysine and by the alpha[66–86] peptide is prevented by spermine. Biochem Biophys Res Commun 194: 83–90, 1993
Romero-Oliva F, Jacob G, Allende JE: Dual effect of lysine-rich polypeptides on the activity of protein kinase CK2. J Cell Biochem 89: 348–355, 2003
Solyakov L, Cain K, Tracey BM, Jukes R, Riley AM, Potter BV, Tobin AB: Regulation of casein kinase-2 (CK2) activity by inositol phosphates. J Biol Chem 279: 4340–4341, 2004
Guerra B, Boldyreff B, Issinger OG: FAS-associated factor 1 interacts with protein kinase CK2 in vivo upon apoptosis induction. Int J Oncol 19: 1117–1126, 2001
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Olsten, M.E.K., Weber, J.E. & Litchfield, D.W. CK2 interacting proteins: Emerging paradigms for CK2 regulation?. Mol Cell Biochem 274, 115–124 (2005). https://doi.org/10.1007/s11010-005-3072-6
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DOI: https://doi.org/10.1007/s11010-005-3072-6