MULTIPLE INDEPENDENT ACTIVATIONS OF THE NEU ONCOGENE BY A POINT MUTATION ALTERING THE TRANSMEMBRANE DOMAIN OF P185
MULTIPLE INDEPENDENT ACTIVATIONS OF THE NEU ONCOGENE BY A POINT MUTATION ALTERING THE TRANSMEMBRANE DOMAIN OF P185
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DOI：
10.1016/0092-8674(86)90779-8
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发表时间：
1986-06-06
期刊：
影响因子：
64.5
通讯作者：
WEINBERG, RA
中科院分区：
文献类型：
--
作者：
BARGMANN, CI;HUNG, MC;WEINBERG, RA
Neu癌基因在BDIX大鼠的神经母细胞瘤和胶质母细胞瘤中经常被激活，最初是在NIH3T3病灶形成试验中发现的。已分离出neu的正常等位基因和转化等位基因的cDNA克隆。当这些克隆插入到表达载体pSV2中时，它们指导neu基因产物p185的合成。转化后的克隆在NIH3T3单层细胞上可产生病灶，而正常的cDNAs则不能。在正常和转化的cDNA之间构建体外重组体，可以确定导致neu原癌基因激活的突变。单点突变将预测蛋白质产物插入的跨膜区中的Valine改变为谷氨酸。来自四个包含激活的neu癌基因的独立细胞系的DNA在这个位置包含相同的突变。
The neu oncogene, which is frequently activated in neuro- and glioblastomas of BDIX rats, was originally identified in the NIH 3T3 focus-forming assay. cDNA clones of the normal and transforming alleles of neu have been isolated. When these clones are inserted into the expression vector pSV2, they direct the synthesis of p185, the neu gene product. The transforming cDNA clone yields foci when transfected onto a NIH 3T3 monolayer, but the normal cDNA does not. The construction of in vitro recombinants between the normal and transforming cDNAs has allowed the determination of the mutation responsible for the activation of the neu proto-oncogene. A single point mutation changes a valine in the transmembrane domain of the predicted protein product insert to a glutamic acid. The DNAs from four independent cell lines containing activated neu oncogenes contain the identical mutation at this position.