Mehmet H, Morris C, Rozengurt E
Growth Regulation Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
Cell Growth Differ. 1990 Jun;1(6):293-8.
The promoter region of the c-fos gene contains several upstream enhancer elements which dictate the transcriptional response to specific intracellular signals. Among these is the cyclic AMP (cAMP)-responsive element, which is required for c-fos expression by cAMP in vitro. However, we have previously shown that cAMP-elevating agents cause only a slight increase in c-fos mRNA levels in intact Swiss 3T3 cells. Here, we show that cAMP can potentiate the induction of c-fos by other second messengers. A combination of forskolin and either phorbol-12,13-dibutyrate or epidermal growth factor leads to an increase in c-fos mRNA levels comparable to those induced by bombesin or serum. Furthermore, cAMP-elevating agents can act in synergy with calcium ionophores (which alone do not induce c-fos) to increase c-fos expression by up to 60% of the bombesin response, although, in parallel cultures, this combination does not stimulate the phosphorylation of 80K, an Mr 80,000 protein, which is a major substrate for protein kinase C. These results suggest that, in intact cells, cAMP acts synergistically with distinct intracellular signals to stimulate c-fos transcription through protein kinase C-dependent and -independent pathways.
c-fos基因的启动子区域包含几个上游增强子元件，这些元件决定了对特定细胞内信号的转录反应。其中包括环磷酸腺苷（cAMP）反应元件，它是体外cAMP诱导c-fos表达所必需的。然而，我们之前已经表明，在完整的瑞士3T3细胞中，升高cAMP的试剂只会使c-fos mRNA水平略有增加。在此，我们表明cAMP可以增强其他第二信使对c-fos的诱导作用。福斯可林与佛波醇-12,13-二丁酸酯或表皮生长因子联合使用，可使c-fos mRNA水平升高，与蛙皮素或血清诱导的水平相当。此外，升高cAMP的试剂可与钙离子载体（单独使用时不会诱导c-fos）协同作用，使c-fos表达增加至蛙皮素反应的60%，尽管在平行培养中，这种组合不会刺激80K（一种分子量为80,000的蛋白质，是蛋白激酶C的主要底物）的磷酸化。这些结果表明，在完整细胞中，cAMP与不同的细胞内信号协同作用，通过蛋白激酶C依赖性和非依赖性途径刺激c-fos转录。
