Differentiation‐dependent switch in protein kinase C isoenzyme activation by FcγRI, the human high‐affinity receptor for immunoglobulin G

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Abstract
Aggregation of receptors for the constant region (Fc) of immunoglobulin G on myeloid cells results in endocytosis or phagocytosis and cellular activation. Previous work has shown, using the cell line U937, that the high-affinity immunoglobulin G receptor, FcγRI, activates alternate intracellular signalling pathways depending on the cell differentiation state, which results in a marked change in the nature of calcium transients within the cell. Here, we show that protein kinase C (PKC) is activated in both interferon-γ (IFN-γ) -primed and dibutyryl cyclic AMP (dbcAMP) -differentiated cells but that the nature of the particular isoenzymes recruited differs. Thus, in IFN-γ-primed U937 cells, FcγRI aggregation results in an increase of PKC activity which is essentially calcium independent resulting from the translocation to the membrane of the novel PKCs, δ and ε, together with the atypical PKC ζ. However, in cells differentiated to a more macrophage phenotype, all PKC enzyme activity after receptor aggregation is calcium dependent. Consistent with this finding, the isoenzymes translocated to the nuclear-free membrane fraction are the conventional PKCs α, β and γ; results consistent with our previous finding that FcγRI couples to phospholipase C in such dbcAMP-differentiated cells. Thus, the nature of PKC isoenzyme activated following FcγRI aggregation is defined by differentiation. The calcium dependence of the PKC isoenzyme is consistent with the duration of calcium transients previously reported in the two differentiation states.