DIFFERENTIAL MODULATION OF PROTEIN-KINASE-C ISOFORMS IN ERYTHROLEUKEMIA DURING INDUCED-DIFFERENTIATION

Induction of erythroid differentiation of murine erythroleukemia cells (MELC) by exposure to hexamethylene bisacetamide (HMBA) involves the modulation of protein kinase C (PKC) activity. Using immuno- and Northern blot techniques, we have demonstrated that MELC express a pattern of PKC isoforms which includes PKCalpha, PKCdelta, PKCepsilon, PKCzeta, and PKCeta. We show that MELC resistant to induction by HMBA express significantly less of the nPKC isoform, PKC delta, and slightly less PKCepsilon. Recovery of HMBA sensitivity is associated with reexpression of PKCdelta protein. Upon exposure to HMBA, there is a fall in cytosolic PKCdelta and PKCepsilon accompanied by a transient increase in membrane-associated forms of these PKC isoforms. HMBA-resistant MELC fail to display this isoform-specific translocation of PKC. Induction of differentiation is accompanied, over the next 24 h of exposure to HMBA, by a progressive fall in cellular PKC activity, associated with a progressive fall in the cellular content of PKCdelta, PKCepsilon, and PKCzeta. These studies suggest that PKCdelta, and possibly PKCepsilon and PKCzeta as well, play a role in the pathway of HMBA-mediated terminal cell differentiation of MELC.