ROLE OF DELTA-PKC ON THE DIFFERENTIATION PROCESS OF MURINE ERYTHROLEUKEMIA-CELLS

In murine erythroleukemia (MEL) cells the length of the latent period before the onset of hexamethylenebisacetamide induced terminal erythroid differentiation is inversely correlated to the intracellular level of δ- PKC. This is supported by the following experimental evidence. V3.17[44] MEL cell line, characterized by a very high rate of differentiation, contains an amount of δ-PKC protein one third lower than that present in the N23 MEL cell line, characterized by a very low rate of differentiation. A similar difference in the amount of δ-PKC mRNA is present in the two cell lines. In N23 cells, following addition of HMBA, the amount of δ-PKC protein and δ- PKC mRNA is down-regulated to one third its original value, which now corresponds to that constitutively present in V3.17[44] cells. Furthermore, in these cells the levels of δ-PKC protein and of its specific mRNA are unaffected by treatment with HMBA. Following introduction of homologous purified δ-PKC both MEL cell variants display a longer latent period before the onset of differentiation: from 50 to 75 hours in N23 cell line and from 20 to 40 hours in V3.17[44] cells, respectively. Taken together, these results suggest that a δ-PKC related signal plays a negative role in the early stages of MEL cell differentiation and that the level of the kinase is controlled through a down-regulation process upon exposure to the chemical inducer.