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

• Using the two-hybrid system, we have screened a D. melanogaster embryo cDNA library for proteins that interact with DmCKIIalpha [8].
• One of the cDNAs isolated in this screen encodes m7, a basic helix-loop-helix (bHLH)-type transcription factor encoded by the Enhancer of split complex (E(spl)C), which regulates neurogenesis. m7 interacts with DmCKIIalpha but not with DmCKIIbeta, suggesting that this interaction is specific for the catalytic subunit of DmCKII [8].
• The striking similarity in molecular structure and catalytic activity between the calf and Drosophila enzyme suggests that casein kinase II has been highly conserved in evolution [9].
• Drosophila CK2 regulates eye morphogenesis via phosphorylation of E(spl)M8 [10].
• In the genome of Drosophila melanogaster, one gene encoding for a CK2alpha subunit and three genes encoding for CK2beta-like proteins are present [11].

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

• We demonstrate that CKIIbeta, beta', and SSL exhibit robust and comparable interaction with CKIIalpha [20].
• Phosphorylation of some of the central oscillator proteins is necessary for the generation of normal circadian rhythms of Drosophila, humans, and Neurospora, where CK1 and CK2 are emerging as the main protein kinases involved in the phosphorylation of PER and FRQ [21].

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].

References