Differentiation-dependent switch in protein kinase C isoenzyme activation by Fc gamma RI, the human high-affinity receptor for immunoglobulin G

Aggregation of receptors for the constant region (Fc) of immunoglobulin G o n myeloid cells results in endocytosis or phagocytosis and cellular activat ion. Previous work has shown, using the cell line U937, that the high-affin ity immunoglobulin G receptor, Fc gamma RI, activates alternate intracellul ar signalling pathways depending on the cell differentiation state, which r esults in a marked change in the nature of calcium transients within the ce ll. Here, we show that protein kinase C (PKC) is activated in both interfer on-gamma (IFN-gamma) -primed and dibutyryl cyclic AMP (dbcAMP) -differentia ted cells but that the nature of the particular isoenzymes recruited differ s. Thus, in IFN-gamma-primed U937 cells, Fc gamma RI aggregation results in an increase of PKC activity which is essentially calcium independent resul ting from the translocation to the membrane of the novel PKCs, delta and ep silon, together with the atypical PKC zeta. However, in cells differentiate d to a more macrophage phenotype, all PKC enzyme activity after receptor ag gregation is calcium dependent. Consistent with this finding, the isoenzyme s translocated to the nuclear-free membrane fraction are the conventional P KCs alpha, beta and gamma; results consistent with our previous finding tha t Fc gamma RI couples to phospholipase C in such dbcAMP-differentiated cell s. Thus, the nature of PKC isoenzyme activated following Fc gamma RI aggreg ation is defined by differentiation. The calcium dependence of the PKC isoe nzyme is consistent with the duration of calcium transients previously repo rted in the two differentiation states.