Lanahan A, Williams J B, Sanders L K, Nathans D
Howard Hughes Medical Institute, Baltimore, Maryland.
Mol Cell Biol. 1992 Sep;12(9):3919-29. doi: 10.1128/mcb.12.9.3919-3929.1992.
Growth factors induce the sequential expression of cellular genes whose products are thought to mediate long-term responses to the growth factors. In mouse 3T3 fibroblastic cells, the first genes to be expressed (immediate-early genes) are activated within minutes after the addition of platelet-derived growth factor, fibroblast growth factor, or serum. By cDNA cloning, we have identified genes that are activated after a delay of a few hours and several hours prior to serum-induced DNA replication. Activation of these delayed early response genes requires new protein synthesis, presumably the synthesis of immediate-early transcription factors described previously. Partial or complete sequencing of 13 different delayed early cDNAs, representing about 40% of the 650 primary cDNA isolates, revealed that 8 were related to known gene sequences and 5 were not. Among the former are cDNAs encoding nonhistone chromosomal proteins [HMGI(Y) and HMGI-C], adenine phosphoribosyltransferase (APRT), a protein related to human macrophage migration inhibitory factor (MIF), a protein of the major intrinsic protein (MIP) family homologous to the integral membrane protein of human erythrocytes, and cyclin CYL1. In 3T3 cells, the delayed early gene response to growth factors appears to be at least as complex as the immediate-early gene response previously described.
生长因子可诱导细胞基因的顺序表达，其产物被认为介导了对生长因子的长期反应。在小鼠3T3成纤维细胞中，最早表达的基因（即早期即刻基因）在添加血小板衍生生长因子、成纤维细胞生长因子或血清后的几分钟内就被激活。通过cDNA克隆，我们鉴定出了一些基因，它们在血清诱导的DNA复制前数小时以及延迟数小时后被激活。这些延迟早期反应基因的激活需要新的蛋白质合成，推测是之前描述的早期即刻转录因子的合成。对13种不同的延迟早期cDNA进行部分或完全测序，这些cDNA约占650个原始cDNA分离物的40%，结果显示其中8种与已知基因序列相关，5种则不相关。前者包括编码非组蛋白染色体蛋白[HMGI(Y)和HMGI-C]、腺嘌呤磷酸核糖转移酶（APRT）、一种与人类巨噬细胞迁移抑制因子（MIF）相关的蛋白质、一种与人类红细胞整合膜蛋白同源的主要内在蛋白（MIP）家族的蛋白质以及细胞周期蛋白CYL1的cDNA。在3T3细胞中，生长因子引发的延迟早期基因反应似乎至少与之前描述的早期即刻基因反应一样复杂。
