Kraft A S, Wagner F, Housey G M
Division of Hematology/Oncology, University of Alabama, Birmingham 35294.
Oncogene. 1990 Aug;5(8):1243-6.
To examine whether overexpression of protein kinase C (PKC) is sufficient to allow for factor-independent growth in hematopoietic cells, we used a recombinant retroviral expression vector system to introduce a cDNA encoding the beta 1 isoform of the PKC gene into IL-3-dependent cells FDC-P1. Cell lines were generated which contained up to 24-fold increases in PKC activity. Analysis of these cell lines demonstrated that PKC activation does not play a significant role in IL-3-mediated growth control, as evidenced by the following: (1) IL-3 addition to either overexpressor cell lines did not induce morphologic changes whereas activators of PKC stimulated cellular clumping; (2) early passage FDC-P1 cells, either carrying normal or elevated levels of PKC, were not stimulated to grow by activators of PKC; and (3) addition of phorbol esters or bryostatin 1 to these cells markedly decreased the levels of PKC without affecting the ability of these cells to grow in IL-3. Therefore, we suggest that IL-3 mediated growth occurs through pathways other than involving PKC.
为了研究蛋白激酶C（PKC）的过表达是否足以使造血细胞实现不依赖生长因子的生长，我们使用重组逆转录病毒表达载体系统，将编码PKC基因β1亚型的cDNA导入依赖白细胞介素-3（IL-3）的细胞FDC-P1中。由此产生的细胞系中PKC活性增加了24倍。对这些细胞系的分析表明，PKC激活在IL-3介导的生长控制中并不起重要作用，证据如下：（1）向任一过表达细胞系中添加IL-3均未诱导形态变化，而PKC激活剂则刺激细胞聚集；（2）早期传代的FDC-P1细胞，无论PKC水平正常还是升高，均未被PKC激活剂刺激生长；（3）向这些细胞中添加佛波酯或苔藓抑素1可显著降低PKC水平，而不影响这些细胞在IL-3中生长的能力。因此，我们认为IL-3介导的生长是通过不涉及PKC的其他途径发生的。
