Lineage commitment of transformed haematopoietic progenitors is determined by the level of PKC activity

摘要: Our previous work showed that haematopoietic precursors transformed by the E26 avian leukemia virus undergo multilineage differentiation in response to phorbol ester 12-myristate 13-acetate (PMA). Treatment of cells with high concentrations PMA (100 nM) favours myelomonocytic differentiation, while lower (20 induce predominantly eosinophil differentiation. Here we have investigated role protein kinase C (PKC) this process and found 100 nM, but not 20 dramatically down-regulates total cellular PKC activity, indicating result less efficient signalling than concentrations. Consistent these findings is observation very low (1 nM), which presumably only moderately activate PKC, myeloid This suggests existence two thresholds play a lineage commitment. To test model, alpha- epsilon-PKC isoforms were expressed E26-transformed progenitors. These exhibited even absence PMA, treatment as nM led eosinophils failed downregulate exogenous PKC. results suggest different levels activity three phenotypes: (i) no maintains progenitor phenotype; (ii) differentiation; (iii)