REGULATION OF PROTEIN-KINASE CKII DURING THE CELL-DIVISION CYCLE

Protein kinase CKII is a prevalent serine/threonine protein kinase who se structure is highly conserved among eukaryotic organisms. Its invol vement in the eukaryotic cell division cycle has been implicated by ge netic experiments in yeast, antisense DNA, and inhibitory antibody exp eriments in mammalian cells, changes in activity during growth stimula tion experiments, and protection of cells from radiation damage to rep licating DNA. In addition, the cdc2 protein kinase, which is central t o cell division cycle control, serves as a substrate for CKII specific ally during the G1 phase of human cells. In this report, extracts of H eLa cells were prepared using neutral, aqueous buffers at low ionic st rength. The cells were enriched for specific stages of the cell divisi on cycle by treatment with drugs or by centrifugal elutriation. The re sults indicate that CKII activity in these extracts is highest during the G1 phase, and there appears to be a reduction in soluble CKII acti vity during the S phase. These data are consistent with the hypothesis that high CKII is necessary for a normal G1 phase but that progressio n through the S phase requires inhibition of CKII.