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 1 h of PMA treatment, while steady-state protein levels increase only slightly. However, within 24 h 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 2 h and 12 h after PMA treatment. Once again, p58^GTA protein kinase activity decreases by 48 h 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.