dsDNA-stimulated phosphorylation of a 72-kDa nucleoprotein accompanies PMA-induced HL-60 leukemic cell differentiation.
PMA treatment of human leukemic cells resulted in a significant increase in the phosphorylation of a 72-kDa protein, which was abrogated by treating the nuclear extracts with DNase I, but additionally stimulated by adding DNA. To be active, DNA must be double-stranded with an average size of 300 base pairs, but shows no apparent species- or sequence-specificity. NP-72 isolated from control or PMA-treated nuclei with 1 mM ATP lacked phosphorylating activity, suggesting it to be a substrate for a dsDNA-stimulated protein kinase(s). Simultaneous exposure of HL-60 cells to PMA and the protein kinase C inhibitor staurosporine diminished the phosphorylation of NP-72. These data suggest that leukemia cell differentiation is accompanied by the induction and/or activation of a dsDNA-stimulated protein kinase whose protein substrates include NP-72 and whose activity is directly or indirectly influenced by protein kinase C.
Konno
S
S
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595.
Wu
J M
JM
D000470:Alkaloids / Q000494:pharmacology; D002454:Cell Differentiation; D004247:DNA / Q000494:pharmacology*; D003851:Deoxyribonucleases / Q000494:pharmacology; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D012260:Ribonucleases / Q000494:pharmacology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D009687:Nuclear Proteins; D004247:DNA; D011494:Protein Kinases; D011493:Protein Kinase C; D003851:Deoxyribonucleases; D012260:Ribonucleases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate