Fujimoto A, Kai S, Akiyama T, Toyoshima K, Kaibuchi K, Takai Y, Yamamoto T
Department of Oncology, University of Tokyo, Japan.
Biochem Biophys Res Commun. 1991 Jul 31;178(2):724-32. doi: 10.1016/0006-291x(91)90168-7.
The mutant c-erbB-2 gene encoding a protein with Glu instead of Val-659 in the transmembrane domain is able to transform NIH3T3 cells, while the wild type c-erbB-2 unless overexpressed does not. The mutant c-erbB-2 protein shows enhanced tyrosine kinase activity in vitro. Transient expression of this active c-erbB-2 stimulated the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element, serum response element, and cyclic AMP response element. Particularly, stimulation of the TPA response element by active c-erbB-2 was prominent. In contrast, transient expression of wild type c-erbB-2 stimulated none of these elements. Transactivation of the TPA response element was also observed in a cell line that stably expresses active c-erbB-2. The active c-erbB-2-induced transactivation of the TPA response element was partially prevented either by down-regulation of protein kinase C or by the protein kinase C inhibitor H7. These results indicate that protein kinase C is partly involved in oncogenic signalling of the active c-erbB-2 protein that leads to Jun/Fos-mediated transcriptional activation in nuclei.
在跨膜结构域编码一种具有谷氨酸而非缬氨酸 - 659的蛋白质的突变型c-erbB-2基因能够转化NIH3T3细胞，而野生型c-erbB-2除非过度表达则不能。突变型c-erbB-2蛋白在体外显示出增强的酪氨酸激酶活性。这种活性c-erbB-2的瞬时表达刺激了12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）反应元件、血清反应元件和环磷酸腺苷反应元件。特别地，活性c-erbB-2对TPA反应元件的刺激很显著。相比之下，野生型c-erbB-2的瞬时表达对这些元件均无刺激作用。在稳定表达活性c-erbB-2的细胞系中也观察到了TPA反应元件的反式激活。活性c-erbB-2诱导的TPA反应元件反式激活部分被蛋白激酶C的下调或蛋白激酶C抑制剂H7所阻止。这些结果表明蛋白激酶C部分参与了活性c-erbB-2蛋白的致癌信号传导，该信号传导导致细胞核中Jun/Fos介导的转录激活。
