Regulation of protein kinase CKII during the cell division cycle.

Abstract

Protein kinase CKII is a prevalent serine/threonine protein kinase whose structure is highly conserved among eukaryotic organisms. Its involvement in the eukaryotic cell division cycle has been implicated by genetic experiments in yeast, antisense DNA, and inhibitory antibody experiments in mammalian cells, changes in activity during growth stimulation experiments, and protection of cells from radiation damage to replicating DNA. In addition, the cdc2 protein kinase, which is central to cell division cycle control, serves as a substrate for CKII specifically during the G1 phase of human cells. In this report, extracts of HeLa cells were prepared using neutral, aqueous buffers at low ionic strength. The cells were enriched for specific stages of the cell division cycle by treatment with drugs or by centrifugal elutriation. The results indicate that CKII activity in these extracts is highest during the G1 phase, and there appears to be a reduction in soluble CKII activity during the S phase. These data are consistent with the hypothesis that high CKII is necessary for a normal G1 phase but that progression through the S phase requires inhibition of CKII.