Regulation of the p58(GTA) cell division control-related protein kinase during phorbol 12-myristate 13-acetate-induced terminal differentiation of U937 cells

We describe the regulation of expression, activity and subcellular localization of a cell cycle control-related kinase, p58(GTA) during the withdrawal from the cell cycle of U937 human leukemic cells induced by phorbol esters. Our studies indicate that steady-state mRNA, protein levels, transcription and subcellular localization of this kinase are affected in distinctly different manners by phorbol esters (phorbol 12-myristate 13-acetate, PMA). Steady-state mRNA levels increase dramatically within 1h of PMA treatment, while steady-state protein levels increase only slightly. However, within 24h of PMA treatment both steady-state p58(GTA) mRNA and protein levels decrease markedly. Assays of p58(GTA) protein kinase activity show that, even though steady-state protein levels are relatively constant, protein kinase activity increases within 30 min of PMA treatment, and then peaks at 2h and 12h after PMA treatment. Once again, p58(GTA) protein kinase activity decreases by 48h to levels similar to unstimulated cells. These results suggest that the expression of the p58(GTA) protein kinase gene and, quite possibly, its post-translational modification are affected by phorbol esters in a complex manner.