Subcellular distribution of cyclic adenosine 3':5'-monophosphate-dependent protein kinase during the chemically induced differentiation of HL-60 cells.

In order to determine if cyclic adenosine 3':5'-monophosphate- (cyclic AMP)-dependent protein kinase has a role in the expression of chemically induced differentiation of HL-60 cells, levels and subcellular distribution of this enzyme were studied during this process. Cyclic AMP binding protein and stimulated kinase activities increased moderately in cytosol and more markedly in nucleosol and nonhistone chromatin-associated protein fractions of cells induced to differentiate with dimethyl sulfoxide or 12-O-tetradecanoylphorbol-13-acetate. Retinoic acid induced similar cytosolic changes but less marked intranuclear increases. Nuclear increases did not occur in the differentiation-resistant subline, HL-60 Blast II, treated with dimethyl sulfoxide. DEAE-cellulose chromatography, as well as photoaffinity labeling and gel electrophoresis, disclosed higher ratios of type I to type II kinase in cytosol than in intranuclear fractions. Differences of the qualitative binding protein patterns between cytosol and nucleosol were enhanced following chemically induced differentiation. Dibutyryl cyclic AMP increased cytoplasmic and nuclear binding protein levels when given alone or in combination with retinoic acid or dimethyl sulfoxide, and it enhanced differentiation. These results suggest that intranuclear cyclic AMP-dependent protein kinase is associated with the expression of the differentiative program in HL-60 cells.