Shibutani M, Lazarovici P, Johnson A C, Katagiri Y, Guroff G
Section on Growth Factors, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 1998 Mar 20;273(12):6878-84. doi: 10.1074/jbc.273.12.6878.
Treatment of PC12 cells with nerve growth factor leads to a decrease in the number of epidermal growth factor receptors on the cell membrane. The mRNA for the epidermal growth factor receptor decreases in a comparable fashion. This decrease appears due to a decrease in the transcription of the epidermal growth factor receptor gene because first, there is no difference in the stability of the epidermal growth factor receptor mRNA, second, newly transcribed epidermal growth factor receptor mRNA is decreased in nerve growth factor-differentiated cells, and third, constructs containing the promoter region of the epidermal growth factor receptor gene are transcribed much less readily in nerve growth factor-differentiated cells than in untreated cells. The decreases in mRNA are not seen in the p140(trk)-deficient variant PC12nnr5 cells nor in cells containing either dominant-negative Ras or dominant-negative Src. Treatment with nerve growth factor also increases the cellular content of GCF2, a putative transcription factor inhibitory for the transcription of the epidermal growth factor receptor gene. The increase in GCF2, like the decrease in the epidermal growth factor receptor mRNA, is not seen in PC12nnr5 cells nor in cells expressing either dominant-negative Ras or dominant-negative Src. The results suggest that nerve growth factor-induced down-regulation of the epidermal growth factor receptor is under transcriptional control, is p140(trk)-, Ras-, and Src-dependent, and may involve transcriptional repression by GCF2.
用神经生长因子处理PC12细胞会导致细胞膜上表皮生长因子受体数量减少。表皮生长因子受体的信使核糖核酸（mRNA）也以类似方式减少。这种减少似乎是由于表皮生长因子受体基因转录减少所致，原因如下：其一，表皮生长因子受体mRNA的稳定性没有差异；其二，在神经生长因子分化的细胞中，新转录的表皮生长因子受体mRNA减少；其三，含有表皮生长因子受体基因启动子区域的构建体在神经生长因子分化的细胞中比在未处理的细胞中更不易转录。在缺乏p140（trk）的PC12nnr5变异细胞以及含有显性负性Ras或显性负性Src的细胞中，未观察到mRNA的减少。用神经生长因子处理还会增加GCF2的细胞含量，GCF2是一种推测对表皮生长因子受体基因转录有抑制作用的转录因子。与表皮生长因子受体mRNA减少的情况一样，在PC12nnr5细胞以及表达显性负性Ras或显性负性Src的细胞中，未观察到GCF2的增加。结果表明，神经生长因子诱导的表皮生长因子受体下调受转录控制，依赖于p140（trk）、Ras和Src，并且可能涉及GCF2的转录抑制作用。
