M-CSF induced differentiation of myeloid precursor cells involves activation of PKC-delta and expression of Pkare

Abstract

Macrophage-colony stimulating factor (M-CSF) regulates proliferation and differentiation of cells belonging to the monocytic lineage. We investigated the mechanisms of M-CSF differentiation signaling in follicular dendritic cell-P1 cells and analyzed the catalytic activation of different protein kinase C (PKC) isoforms. M-CSF induced rapid catalytic activation of PKC-delta and membrane translocation of the tyrosine phosphorylated form of PKC-delta. Mutation of tyrosine 807 in the M-CSF receptor (Fms) abrogates cell differentiation but not a proliferative response to M-CSF, and FmsY807F failed to activate PKC-delta. We also investigated the downstream signaling pathways from PKC-delta. A cyclic adenosine monophosphate-regulated Ser/Thr kinase gene, protein kinase X (PRKX), has been associated with macrophage differentiation in human cells. We found that M-CSF and PKC-delta induced the expression of the PRKX murine homologue: PKA-related gene. Taken together, our results indicate that PKC-delta functions as a critical mediator of M-CSF-induced differentiation signaling.