Expression and regulation of protein kinase CK2 during the cell cycle

There are indications from genetic, biochemical and cell biological studies that protein kinase CK2 (formerly casein kinase II) has a variety of funct ions at different stages in the cell cycle. To further characterize CK2 and its potential roles during cell cycle progression, one of the objectives o f this study was to systematically examine the expression of all three subu nits of CK2 at different stages in the cell cycle. To achieve this objectiv e, we examined levels of CK2 alpha, CK2 alpha' and CK2 beta on immunoblots as well as CK2 activity in samples prepared from: (i) elutriated population s of MANCA (Burkitt lymphoma) cells, (ii) serum-stimulated GL30-92/R (prima ry human fibroblasts) cells and (iii) drug-arrested chicken bursal lymphoma BK3A cells. On immunoblots, we observed a significant and co-ordinate incr ease in the expression of CK2 alpha and CK2 alpha' following serum stimulat ion of quiescent human fibroblasts. By comparison, no major fluctuations in CK2 activity were detected during any other stages during the cell cycle. Furthermore, we did not observe any dramatic differences between the relati ve levels of CK2 alpha to CK2 alpha' during different stages in the cell cy cle. However, we observed a significant increase in the amount of CK2 beta relative to CK2 alpha in cells arrested with nocodazole. We also examined t he activity of CK2 in extracts or in immunoprecipitates prepared from drug- arrested cells. Of particular interest is the observation that the activity of CK2 is not changed in nocodazole-arrested cells. Since CK2 is maximally phosphorylated in these cells, this result suggests that the phosphorylati on of CK2 by p34(cdc2) does not affect the catalytic activity of CK2. Howev er, the activity of CK2 was increased by incubation with p34(cdc2) in vitro . Since this activation was independent of ATP we speculate that p39(cdc2) may have an associated factor that stimulates CK2 activity. Collectively, t he observations that relative levels of CK2 beta increase in mitotic cells, that CK2 alpha: and CK2 beta are phosphorylated in mitotic cells and that p34(cdc2) affects CK2 activity in vitro suggest that CK2 does have regulato ry functions associated with cell division.