Casein kinases: pleiotropic mediators of cellular regulation.

The present review on casein kinases focuses mainly on the possible metabolic role of CK-2, with special emphasis on its behavior in pathological tissues. From these data at least three ways to regulate CK-2 activity emerge: (i) CK-2 activity changes during embryogenesis, being high at certain stages of development and showing basal activity values at others; (ii) CK-2 activity can be enhanced in vitro by treatment of tissue culture cells with various growth factors and serum and (iii) CK-2 activity is constitutively enhanced in rapidly proliferating cells. The regulated CK-2 activity changes during embryogenesis cannot be explained as yet. In the case of the constitutive high expression of CK-2 in tumors, genetic changes may be responsible, e.g. through alterations of the regulatory genetic elements and/or regulation by specific transcription factors. In the case of serum induction, no genetic changes are necessarily involved; the observed changes may be entirely due to a signal transduction pathway where CK-2 could be phosphorylated by another kinase(s). CK-2 cDNAs from various organisms have been isolated and characterized. From the deduced amino acid sequence it turns out that CK-2 subunits are highly conserved during evolution. The relationship between CK-2 alpha from humans and plants is still 73%. Similar relationships are reported for the beta-subunit. Chromosomal assignment of CK-2 alpha shows two gene loci, one of which is a pseudogene. They are located on different chromosomes. Expression of the CK-2 subunits in Escherichia coli and the Baculo expression system is shown. The recombinant subunits can self-assemble to a functional holoenzyme in vitro. Biochemical and biophysical analysis of the recombinant beta-subunit suggests it to be trifunctional in association with the alpha-subunit affecting: (i) stability, (ii) enzyme specificity and (iii) enzyme activity. The question where CK-2 and its subunits are located throughout the cell cycle has also been addressed, mainly because of the large discrepancies that still exist between results obtained by different investigators. Tissue-specific expression of CK-2 at the mRNA and at the protein level has also been given attention. The fact that the enzyme activity is surprisingly high in brain and low in heart and lung may be indicative of involvement of CK-2 in processes other than proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)