Phorbol diester-induced alterations in the expression of protein kinase C isozymes and their mRNAs. Analysis in wild-type and phorbol diester-resistant HL-60 cell clones.

摘要: Abstract In an HL-60 cell subline (PR-17) which was greater than 100-fold resistant to the differentiating and cytostatic activities of phorbol 12-myristate 13-acetate (PMA), protein kinase C phenotype found be nearly identical that wild-type cells. A measurable decrease (30%) in specific crude preparations PR-17 observed when enzyme measured with histone as phosphate acceptor substrate, but other aspects (intracellular concentrations binding affinities diester receptors, translocation activated from cytosolic particulate subcellular fractions, relative expression alpha beta isozyme proteins) were equivalent both PMA-resistant cells Direct analysis behavior isozymes after exposure each type 100 nM PMA for 12 h revealed intracellular downregulated extent These results suggest cellular basis resistance effects present "down-stream" activation down-regulation perhaps a nuclear component. Among genes likely differentially regulated two lines treated those themselves. cells, mRNA increased (up 5-fold) 48 initiation treatment; further studies indicate activator could influence isozyme-specific manner. Comparable PMA-induced alterations levels not even under conditions significant subsequent protein. Taken together, these data may represent absolute determinants differentiation C, or by isozymes, are important induction leukemia PMA.