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Gene Review

CkIIalpha  -  casein kinase IIalpha

Drosophila melanogaster

Synonyms: 0958/08, CG17520, CJIIalpha, CK II, CK II subunit alpha, ...
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Disease relevance of CkIIalpha

  • The cloning and expression of rabbit CK-II will allow us to generate antibody and cDNA probes to investigate the role of CK-II in VSMC growth, migration, and phenotypic transformation during the pathogenesis of vascular disease [1].
  • Renaturation of casein kinase II from recombinant subunits produced in Escherichia coli: purification and characterization of the reconstituted holoenzyme [2].
  • Expression and purification of the alpha and beta subunits of Drosophila casein kinase II using a baculovirus vector [3].

High impact information on CkIIalpha

  • Here we show that the catalytic subunit of Drosophila casein kinase 2 (CK2alpha) is expressed predominantly in the cytoplasm of key circadian pacemaker neurons [4].
  • Phosphorylation by PKC but not by casein kinase II enhances the GTPase activity of dynamin 12-fold [5].
  • Using an in vivo assay a form of ANTP that has alanine substitutions at its CKII target sites has, in addition to wild-type ANTP functions, the ability to alter severely thoracic and abdominal development [6].
  • Our results suggest that phosphorylation of ANTP by CKII is important for preventing inappropriate activities of this homeotic protein during embryogenesis [6].
  • In contrast, the in vivo activity of a form of ANTP that contains acidic amino acid substitutions at its CKII target sites, thereby mimicking a constitutively phosphorylated ANTP protein, is greatly reduced [6].

Chemical compound and disease context of CkIIalpha

  • The catalytic (alpha) subunit of casein kinase II from Drosophila, cloned and expressed in Escherichia coli (Saxena, A., Padmanabha, R., and Glover, C. V. C., (1987) Mol. Cell. Biol. 7, 3409-3417), has been purified and characterized, and the properties have been compared to those of the holoenzyme [7].

Biological context of CkIIalpha


Anatomical context of CkIIalpha

  • Similarities in structure and function of calf thymus and Drosophila casein kinase II [9].
  • Using the yeast two-hybrid system and coimmunoprecipitation analysis of protein extract from Drosophila testes, we demonstrated an association between CK2(beta)tes and CK2alpha [12].
  • Experiments in our laboratory have shown a marked increase of casein kinase II- (CK II-) like activity in T. parva-transformed lymphocytes [13].
  • Our data demonstrate expression of the CKIIalpha intronless gene in megakaryocytes and platelets [14].
  • This confirmed that the two human T-cell cDNA clones encoded the alpha and alpha' subunits of casein kinase II [15].

Associations of CkIIalpha with chemical compounds

  • Finally, substitution of Ser(159) of m8 with Ala attenuates interaction with DmCKIIalpha, whereas substitution with Asp abolishes the interaction [8].
  • The weak phosphorylation by CK2alpha is markedly stimulated by the activator polylysine to levels comparable to those with the holoenzyme [16].
  • Biochemical analyses using gel filtration analysis, inhibitor and heat treatment, as well as urea denaturation studies did not yield significant differences between the wildtype holoenzyme (alpha2beta2) and a holoenzyme containing wildtype CK2alpha and andante CK2beta(And) [17].
  • Overexpression of CKII reduced transcriptional repression by mCut, whereas a mutant mCut protein containing alanine substitutions at these sites was not affected [18].
  • Our laboratory reported yeast CKII to be composed of four polypeptides of 42, 41, 35, and 32 kDa (R. Padmanabha and C. V. C. Glover, 1987, J. Biol. Chem. 262, 1829-1835) [19].

Enzymatic interactions of CkIIalpha

  • We demonstrate that Dpn is weakly phosphorylated by monomeric CK2alpha, whereas it is robustly phosphorylated by the embryo-holoenzyme, suggesting a positive role for CK2beta [16].

Other interactions of CkIIalpha


Analytical, diagnostic and therapeutic context of CkIIalpha

  • Sequence analysis of Cut repeats revealed the presence of sequences that match the consensus phosphorylation site for casein kinase II (CKII) [18].
  • Casein kinase II of yeast has been purified to near homogeneity by a procedure which includes affinity chromatography on heparin-agarose [22].
  • In western blot analyses, only the alpha subunit reacts strongly with polyclonal antibodies to a Drosophila casein kinase II [23].
  • PCR cloning and sequence of two cDNAs encoding the alpha and beta subunits of rabbit casein kinase-II [1].
  • The procedure was first successfully used for the purification of CK2 from the Drosophila melanogaster cell culture [24].


  1. PCR cloning and sequence of two cDNAs encoding the alpha and beta subunits of rabbit casein kinase-II. Gupta, S.K., Singh, J.P. Gene (1993) [Pubmed]
  2. Renaturation of casein kinase II from recombinant subunits produced in Escherichia coli: purification and characterization of the reconstituted holoenzyme. Lin, W.J., Traugh, J.A. Protein Expr. Purif. (1993) [Pubmed]
  3. Expression and purification of the alpha and beta subunits of Drosophila casein kinase II using a baculovirus vector. Birnbaum, M.J., Wu, J., O'Reilly, D.R., Rivera-Marrero, C.A., Hanna, D.E., Miller, L.K., Glover, C.V. Protein Expr. Purif. (1992) [Pubmed]
  4. A role for casein kinase 2alpha in the Drosophila circadian clock. Lin, J.M., Kilman, V.L., Keegan, K., Paddock, B., Emery-Le, M., Rosbash, M., Allada, R. Nature (2002) [Pubmed]
  5. Dynamin GTPase regulated by protein kinase C phosphorylation in nerve terminals. Robinson, P.J., Sontag, J.M., Liu, J.P., Fykse, E.M., Slaughter, C., McMahon, H., Südhof, T.C. Nature (1993) [Pubmed]
  6. A role for phosphorylation by casein kinase II in modulating Antennapedia activity in Drosophila. Jaffe, L., Ryoo, H.D., Mann, R.S. Genes Dev. (1997) [Pubmed]
  7. Characterization of the catalytic subunit of casein kinase II expressed in Escherichia coli and regulation of activity. Lin, W.J., Tuazon, P.T., Traugh, J.A. J. Biol. Chem. (1991) [Pubmed]
  8. Drosophila melanogaster casein kinase II interacts with and phosphorylates the basic helix-loop-helix proteins m5, m7, and m8 derived from the Enhancer of split complex. Trott, R.L., Kalive, M., Paroush, Z., Bidwai, A.P. J. Biol. Chem. (2001) [Pubmed]
  9. Similarities in structure and function of calf thymus and Drosophila casein kinase II. Dahmus, G.K., Glover, C.V., Brutlag, D.L., Dahmus, M.E. J. Biol. Chem. (1984) [Pubmed]
  10. Drosophila CK2 regulates eye morphogenesis via phosphorylation of E(spl)M8. Karandikar, U.C., Trott, R.L., Yin, J., Bishop, C.P., Bidwai, A.P. Mech. Dev. (2004) [Pubmed]
  11. The Drosophila melanogaster DmCK2beta transcription unit encodes for functionally non-redundant protein isoforms. Jauch, E., Wecklein, H., Stark, F., Jauch, M., Raabe, T. Gene (2006) [Pubmed]
  12. CK2(beta)tes gene encodes a testis-specific isoform of the regulatory subunit of casein kinase 2 in Drosophila melanogaster. Kalmykova, A.I., Shevelyov, Y.Y., Polesskaya, O.O., Dobritsa, A.A., Evstafieva, A.G., Boldyreff, B., Issinger, O.G., Gvozdev, V.A. Eur. J. Biochem. (2002) [Pubmed]
  13. Cloning and characterization of the casein kinase II alpha subunit gene from the lymphocyte-transforming intracellular protozoan parasite Theileria parva. ole-MoiYoi, O.K., Sugimoto, C., Conrad, P.A., Macklin, M.D. Biochemistry (1992) [Pubmed]
  14. Sequencing of full-length cDNA encoding the alpha and beta subunits of human casein kinase II from human platelets and megakaryocytic cells. Expression of the casein kinase IIalpha intronless gene in a megakaryocytic cell line. Singh, L.S., Kalafatis, M. Biochemistry (2002) [Pubmed]
  15. Isolation and characterization of human cDNA clones encoding the alpha and the alpha' subunits of casein kinase II. Lozeman, F.J., Litchfield, D.W., Piening, C., Takio, K., Walsh, K.A., Krebs, E.G. Biochemistry (1990) [Pubmed]
  16. Drosophila CK2 phosphorylates Deadpan, a member of the HES family of basic-helix-loop-helix (bHLH) repressors. Karandikar, U.C., Shaffer, J., Bishop, C.P., Bidwai, A.P. Mol. Cell. Biochem. (2005) [Pubmed]
  17. Biochemical characterization of the recombinant human Drosophila homologues Timekeeper and Andante involved in the Drosophila circadian oscillator. Rasmussen, T., Skjøth, I.H., Jensen, H.H., Niefind, K., Boldyreff, B., Issinger, O.G. Mol. Cell. Biochem. (2005) [Pubmed]
  18. DNA binding by cut homeodomain proteins is down-modulated by casein kinase II. Coqueret, O., Martin, N., Bérubé, G., Rabbat, M., Litchfield, D.W., Nepveu, A. J. Biol. Chem. (1998) [Pubmed]
  19. Casein kinase II of Saccharomyces cerevisiae contains two distinct regulatory subunits, beta and beta'. Bidwai, A.P., Reed, J.C., Glover, C.V. Arch. Biochem. Biophys. (1994) [Pubmed]
  20. The Drosophila SSL gene is expressed in larvae, pupae, and adults, exhibits sexual dimorphism, and mimics properties of the beta subunit of casein kinase II. Karandikar, U., Anderson, S., Mason, N., Trott, R.L., Bishop, C.P., Bidwai, A.P. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  21. CK2 phosphorylation of CCA1 is necessary for its circadian oscillator function in Arabidopsis. Daniel, X., Sugano, S., Tobin, E.M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  22. Casein kinase II of yeast contains two distinct alpha polypeptides and an unusually large beta subunit. Padmanabha, R., Glover, C.V. J. Biol. Chem. (1987) [Pubmed]
  23. Purification and characterization of a casein kinase 2-type protein kinase from pea nuclei. Li, H., Roux, S.J. Plant Physiol. (1992) [Pubmed]
  24. Phosphorylation of the protein encoded by the first open reading frame of the MDG4 transposable element (gypsy) by homologous and heterologous casein kinases type 2. Malikova, M.A., Syomin, B.V., Stepanov, A.S. Biochemistry Mosc. (2001) [Pubmed]
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