Mechanisms of signaling from cell surface receptors to nuclear genes.

众所周知，一些核基因的表达是由细胞外信号通过其细胞表面受体调节的。然而，从细胞表面受体到核基因的信号传导机制还没有基本上阐明。在本研究项目中，我们研究了Swiss 3 T3细胞中PDGF、FGF、prostaglandin<E_1>（<PGE_1>）和EGF受体对c-myc和c-fos基因的信号传导机制。PDGF、FGF<PGE_1>和EGF是该细胞系的有效生长因子。在Balb/c 3 T3细胞中，c-myc和c-fos基因被认为是负责细胞周期从0期向0期转变的基因<G_0><G_1>。我们的一系列实验表明，PDGF和FGF通过蛋白激酶C激活和&lt;Ca^（2+）&gt;动员激活c-myc和c-fos基因，这两者都是由磷脂酶C以受体连接的方式介导的磷酸肌醇水解诱导的。相反，<PGE_1>通过环腺苷酸的产生和&lt;Ca^（2+）&gt;内流激活这些基因。在EGF的情况下，这种生长因子也激活这些基因，但这种生长因子的信号传导机制仍然未知。这些结果表明，至少有三个细胞内信使系统，蛋白激酶C，&lt;Ca^（2+）&gt;和环AMP，它们参与了生长因子诱导的Swiss 3 T3细胞c-myc和c-fos基因的表达。另一系列实验已经阐明，蛋白激酶C参与抑制瑞士3 T3细胞中FGF诱导的磷脂酶C反应和β<PGE_1>-诱导的&lt;Ca^（2+）&gt;内流。这些观察结果与上述结果一起表明，蛋白激酶C在该细胞系中对生长因子诱导的c-myc和c-fos基因表达不仅起正调节作用，而且起负调节作用。

It is well known that expression of some nuclear genes is regulated by extracellular signals through their cell surface receptors. However, the mechanisms of signaling from the cell surface receptors to the nuclear genes have not been substantially clarified. In this research project, we have investigated the mechanisms of signaling from the receptors for PDGF, FGF, prostaglandin <E_1> ( <PGE_1> ) and EGF to the c-myc and c-fos genes in Swiss 3T3 cells. PDGF, FGF, <PGE_1> and EGF are potent growth factors for this cell line. The c-myc and c-fos genes have been suggested to be responsible for the transition from the <G_0> to <G_1> phase of the cell cycle in Balb/c 3T3 cells. Our series of experiments have revealed that PDGF and FGF activate the c-myc and c-fos genes through the protein kinase C activation and <Ca^(2+)> mobilization, both of which are induced by the phospholipase C-mediated hydrolysis of phosphoinositides in a receptor-linked manner. In contrast, <PGE_1> activates these genes through cyclic AMP production and <Ca^(2+)> influx. In the case of EGF, this growth factor also activates these genes, but the signaling mechanism of this growth factor is still unknown. These results indicate that there are at least three intracellular messenger systems, protein kinase C, <Ca^(2+)> and cyclic AMP, which are involved in the growth factor-induced expression of the c-myc and c-fos genes in Swiss 3T3 cells. Another series of experiments have clarified that protein kinase C is involved in inhibition of the FGF-induced phospholipase C reaction and the <PGE_1> -induced <Ca^(2+)> influx in Swiss 3T3 cells. These observations together with the results described above suggest that protein kinase C acts as not only a positive but also a negative regulator for the growth factor-induced expression of the c-myc and c-fos genes in this cell line.