Protein Kinase C in Cell Growth and Differentiation
It has been shown that human promyelocytic leukemia cell line HL601 and acute myeloblastic leukemia cell line KG-12 can be induced to terminally differentiate to macrophage-like cells by 12-0-tetradecanoylphorbol-13-acetate (TPA). Because TPA is a potent activator of protein kinase C (PKC) and the enzyme is the only known high affinity receptor for the tumor promoter3, it is likely that the TPA effects are PKC-dependent. TPA, however, is ineffective in inducing differentiation of a HL60 subline HL60BII4 and a KG-1 subline KG-1a5. The molecular mechanisms underlying the responsiveness or resistance to the differentiating effect of TPA remain unclear. The density and affinity of cell surface receptors for phorbol ester appear to be uninvolved, because there are no significant differences in the binding properties of phorbol ester between KG-1 and KG-1a cells6 or between HL60 and HL60BII cells4. The post-receptor events that occur after binding of TPA to the plasma membrane PKC, which might be distinct for the sublines, perhaps are critical in determining the sensitivity of cells to the differentiating effect of TPA. In this paper we summarize our recent studies on the PKC system in these and other cell lines as well as in developing nervous tissues, aiming to elucidate a role of PKC in cell growth and differentiation.
KeywordsHL60 Cell Phorbol Ester Differentiate Effect HL60 Cell Differentiation Human Promyelocytic Leukemia Cell Line
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