A deletion mutation within the ligand binding domain is responsible for activation of epidermal growth factor receptor gene in human brain tumors.
A deletion mutation within the ligand binding domain is responsible for activation of epidermal growth factor receptor gene in human brain tumors.
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DOI：
10.1111/j.1349-7006.1990.tb02644.x
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发表时间：
1990-08
期刊：
影响因子：
--
通讯作者：
Shibuya M
中科院分区：
文献类型：
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作者：
Yamazaki H;Ohba Y;Tamaoki N;Shibuya M
人多形性胶质母细胞瘤GL-3和GL-5的两个可移植细胞系携带结构改变的表皮生长因子（EGF）受体基因的扩增和过表达：在这些情况下，140千道尔顿的EGF受体表现出组成型表达的酪氨酸激酶活性，而不含配体。在这里，我们从GL-5细胞系中分离出异常的EGF受体cDNA，并证明该cDNA在EGF受体的配体结合结构域内具有一个长801个碱基对的分子内缺失突变。在其他区域中未观察到氨基酸取代。在基因组DNA水平上，这种缺失似乎从EGF受体基因的第1内含子开始，终止于第6内含子。然而，在胶质母细胞瘤的两个细胞系GL-3和GL-5中，这些内含子中缺失突变的起始或结束位置并不相同，这表明在缺失突变的形成中涉及独特的重组机制。在缺失携带EGF受体cDNA中观察到弱但不依赖配体的转化活性。
Two transplantable cell lines of human glioblastoma multiforme GL‐3 and GL‐5 carried an amplification and overexpression of structurally altered epidermal growth factor (EGF) receptor gene: the 140 kilodalton EGF receptors in these cases exhibited a constitutively expressed tyrosine kinase activity without the ligand. Here, we isolated the abnormal EGF receptor cDNA from GL‐5 cell line, and demonstrated that this cDNA bears a single large intramolecular deletion mutation 801 base pairs long within the ligand binding domain of EGF receptor. In other regions no amino acid substitution was observed. At the level of genomic DNA, this deletion appeared to start from the 1st intron and terminate in the 6th intron of the EGF receptor gene. However, in the two lines of glioblastoma, GL‐3 and GL‐5, the positions of the start or the end of the deletion mutation in these introns were not identical, suggesting an involvement of a unique recombination mechanism in the formation of deletion mutation. A weak but ligand‐independent transforming activity was observed in the deletion‐carrying EGF receptor cDNA.