Leng L, Yu F, Dong L, Busquets X, Osada S, Richon V M, Marks P A, Rifkind R A
DeWitt Wallace Laboratory for Developmental Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer Res. 1993 Nov 15;53(22):5554-8.
Induction of erythroid differentiation of murine erythroleukemia cells (MELC) by exposure to hexamethylene bisacetamide (HMBA) involves the modulation of protein kinase C (PKC) activity. Using immuno- and Northern blot techniques, we have demonstrated that MELC express a pattern of PKC isoforms which includes PKC alpha, PKC delta, PKC epsilon, PKC zeta, and PKC eta. We show that MELC resistant to induction by HMBA express significantly less of the nPKC isoform, PKC delta, and slightly less PKC epsilon. Recovery of HMBA sensitivity is associated with reexpression of PKC delta protein. Upon exposure to HMBA, there is a fall in cytosolic PKC delta and PKC epsilon accompanied by a transient increase in membrane-associated forms of these PKC isoforms. HMBA-resistant MELC fail to display this isoform-specific translocation of PKC. Induction of differentiation is accompanied, over the next 24 h of exposure to HMBA, by a progressive fall in cellular PKC activity, associated with a progressive fall in the cellular content of PKC delta, PKC epsilon, and PKC zeta. These studies suggest that PKC delta, and possibly PKC epsilon and PKC zeta as well, play a role in the pathway of HMBA-mediated terminal cell differentiation of MELC.
通过暴露于六亚甲基双乙酰胺（HMBA）诱导小鼠红白血病细胞（MELC）向红细胞分化涉及蛋白激酶C（PKC）活性的调节。运用免疫印迹和Northern印迹技术，我们已证明MELC表达的PKC同工型模式包括PKCα、PKCδ、PKCε、PKCζ和PKCη。我们发现对HMBA诱导有抗性的MELC表达的nPKC同工型PKCδ显著减少，PKCε略有减少。HMBA敏感性的恢复与PKCδ蛋白的重新表达相关。暴露于HMBA后，胞质PKCδ和PKCε减少，同时这些PKC同工型的膜相关形式短暂增加。对HMBA有抗性的MELC未能表现出这种PKC的同工型特异性易位。在接下来暴露于HMBA的24小时内，分化诱导伴随着细胞PKC活性的逐渐下降，这与PKCδ、PKCε和PKCζ的细胞含量逐渐下降相关。这些研究表明PKCδ，可能还有PKCε和PKCζ，在HMBA介导的MELC终末细胞分化途径中起作用。
