Lacal J C, Cuadrado A, Jones J E, Trotta R, Burstein D E, Thomson T, Pellicer A
Instituto de Investigaciones Biomedicas, Madrid, Spain.
Mol Cell Biol. 1990 Jun;10(6):2983-90. doi: 10.1128/mcb.10.6.2983-2990.1990.
Expression of the N-ras oncogene under the control of the glucocorticoid-responsive promoter in the pheochromocytoma cell line UR61, a subline of PC-12 cells, has been used to investigate the differentiation process to neuronal cells triggered by ras oncogenes (I. Guerrero, A. Pellicer, and D. E. Burstein, Biochem. Biophys. Res. Commun. 150:1185-1192, 1988). Using ras-inducible cell lines, we observed that expression of the oncogenic N-ras p21 protein interferes with the ability of phorbol esters to induce downregulation of protein kinase C. This effect was associated with the appearance of immunologically detectable protein kinase C as well as the activity of the enzyme as analyzed either by binding of [3H]phorbol-12,13-dibutyrate in intact cells or by in vitro kinase activity. These results indicate a relationship between ras p21 and protein kinase C in neuronal differentiation in this model system. Comparison to the murine fibroblast system suggests that this relationship may be functional.
在嗜铬细胞瘤细胞系UR61（PC - 12细胞的一个亚系）中，N - ras癌基因在糖皮质激素反应性启动子的控制下表达，已被用于研究由ras癌基因触发的向神经元细胞的分化过程（I. 格雷罗、A. 佩利塞和D. E. 伯斯坦，《生物化学与生物物理学研究通讯》150:1185 - 1192，1988）。使用ras诱导细胞系，我们观察到致癌性N - ras p21蛋白的表达会干扰佛波酯诱导蛋白激酶C下调的能力。这种效应与免疫可检测的蛋白激酶C的出现以及该酶的活性相关，这一活性通过完整细胞中[³H]佛波醇 - 12,13 - 二丁酸的结合或体外激酶活性进行分析。这些结果表明在该模型系统的神经元分化中ras p21与蛋白激酶C之间存在一种关系。与小鼠成纤维细胞系统的比较表明这种关系可能具有功能。
