Kamada S, Toyoshima K, Akiyama T
Department of Oncogene Research, Osaka University, Japan.
J Biol Chem. 1994 Feb 11;269(6):4565-70.
To understand the mechanisms regulating the transactivating activity of Jun/AP-1, we analyzed alterations in c-Jun induced by growth stimulation and cell transformation. Serum stimulation of quiescent NIH3T3 cells induced a marked increase in phosphorylation of c-Jun in its amino-terminal activation domain. On the other hand, this domain was highly phosphorylated, in a serum-independent manner, in cells transformed with various oncogenes, including active c-raf-1, v-src, active Ha-ras, and active erbB-2. There were no obvious differences in the phosphorylation states of c-Jun in exponentially growing normal and transformed cells. However, in the exponentially growing state, the TRECAT activity in transformed cells was markedly higher than that in normal cells. Gel retardation analysis indicated that the AP-1 components in transformed cells were significantly different from those in normal cells. These results suggest that some other alterations besides phosphorylation of c-Jun are involved in enhancement of AP-1 activity in exponentially growing transformed cells.
为了解调节Jun/AP-1反式激活活性的机制，我们分析了生长刺激和细胞转化诱导的c-Jun的变化。血清刺激静止的NIH3T3细胞会导致c-Jun氨基末端激活域的磷酸化显著增加。另一方面，在用包括活性c-raf-1、v-src、活性Ha-ras和活性erbB-2在内的各种癌基因转化的细胞中，该结构域以不依赖血清的方式高度磷酸化。在指数生长的正常细胞和转化细胞中，c-Jun的磷酸化状态没有明显差异。然而，在指数生长状态下，转化细胞中的TRECAT活性明显高于正常细胞。凝胶阻滞分析表明，转化细胞中的AP-1成分与正常细胞中的显著不同。这些结果表明，除了c-Jun的磷酸化外，其他一些变化也参与了指数生长的转化细胞中AP-1活性的增强。
