Bargmann C I, Hung M C, Weinberg R A
Nature. 1986;319(6050):226-30. doi: 10.1038/319226a0.
The neu oncogene is repeatedly activated in neuro- and glioblastomas derived by transplacental mutagenesis of the BDIX strain of rat with ethylnitrosourea. Foci induced by the DNAs from such tumours on NIH 3T3 cells contain the neu oncogene and an associated phosphoprotein of relative molecular mass 185,000 (p185). Previous work has shown that the neu gene is related to, but distinct from, the gene encoding the EGF receptor (c-erb-B). Here we describe a neu complementary DNA clone isolated from a cell line transformed by this oncogene; the clone has biological activity in a focus-forming assay. The nucleotide sequence of this clone predicts a 1,260-amino-acid transmembrane protein product similar in overall structure to the EGF receptor. We found that 50% of the predicted amino acids of neu and the EGF receptor are identical; greater than 80% of the amino acids in the tyrosine kinase domain are identical. Our results suggest strongly that the neu gene encodes the receptor for an as yet unidentified growth factor.
通过用乙基亚硝基脲对大鼠BDIX品系进行经胎盘诱变而产生的神经母细胞瘤和胶质母细胞瘤中,neu癌基因会反复被激活。来自此类肿瘤的DNA在NIH 3T3细胞上诱导形成的病灶含有neu癌基因和一种相对分子质量为185,000的相关磷蛋白(p185)。先前的研究表明,neu基因与编码表皮生长因子受体(c-erb-B)的基因相关,但又有所不同。在此,我们描述了从由该癌基因转化的细胞系中分离出的一个neu互补DNA克隆;该克隆在焦点形成试验中具有生物学活性。这个克隆的核苷酸序列预测出一种1260个氨基酸的跨膜蛋白产物,其整体结构与表皮生长因子受体相似。我们发现neu和表皮生长因子受体预测的氨基酸中有50%是相同的;酪氨酸激酶结构域中超过80%的氨基酸是相同的。我们的结果有力地表明,neu基因编码一种尚未确定的生长因子的受体。