SIMILARITY OF PROTEIN ENCODED BY THE HUMAN C-ERB-B-2 GENE TO EPIDERMAL GROWTH-FACTOR RECEPTOR

SIMILARITY OF PROTEIN ENCODED BY THE HUMAN C-ERB-B-2 GENE TO EPIDERMAL GROWTH-FACTOR RECEPTOR
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DOI:
10.1038/319230a0
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发表时间:
1986-01-16
期刊:
影响因子:
64.8
通讯作者:
TOYOSHIMA, K
TOYOSHIMA, K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
YAMAMOTO, T;IKAWA, S;TOYOSHIMA, K

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一个新的v- erbb - b相关基因,c- erbb -2,已经在人类基因组中被发现1,2,定位于人类17号染色体q21处(参考文献40),并且似乎编码一个激酶结构域的多肽,该激酶结构域与表皮生长因子(EGF)受体高度同源,但不同于表皮生长因子受体1。c- erbb -2基因在脊椎动物中是保守的,有人认为,在一系列大鼠神经/胶质母细胞瘤中检测到的基因实际上是大鼠c- erbb -2基因。c- erbb -2基因在唾液腺癌和胃癌细胞系MKN-7中的扩增表明其过度表达有时参与肿瘤过程。为了确定c- erbb -2蛋白的性质,我们现在克隆了从MKN-7细胞中制备的c- erbb -2信使RNA的互补DNA。它的序列表明c- erbb - b- 2基因编码一种可能的受体蛋白,并允许分析该蛋白与EGF受体和新产物的相似性。在MKN-7细胞中,由于染色体畸变,c- erbb -2的4.6 kb正常转录本和截断的2.3 kb转录本在高水平上合成。后一种转录物可能只编码假定受体的细胞外结构域。
A novel v-erb-B-related gene, c-erb-B-2, which has been identified in the human genome1,2, maps to human chromosome 17 at q21 (ref. 40), and seems to encode a polypeptide with a kinase domain that is highly homologous with, but distinct from, that of the epidermal growth factor (EGF) receptor1. The c-erb-B-2 gene is conserved in vertebrates and it has been suggested1 that theneugene, detected in a series of rat neuro/glioblastomas3, is, in fact, the rat c-erb-B-2 gene. Amplification of the c-erb-B-2 gene in a salivary adenocarcinoma and a gastric cancer cell line MKN-7 suggests that its over-expression is sometimes involved in the neoplastic process. To determine the nature of the c-erb-B-2 protein, we have now molecularly cloned complementary DNA for c-erb-B-2 messenger RNA prepared from MKN-7 cells. Its sequence shows that the c-erb-B-2 gene encodes a possible receptor protein and allows an analysis of the similarity of the protein to the EGF receptor and theneuproduct. As a consequence of chromosomal aberration in MKN-7 cells, a 4.6-kilobase (kb) normal transcript and a truncated 2.3-kb transcript of c-erb-B-2 are synthesized at elevated levels. The latter transcript presumably encodes only the extracellular domain of the putative receptor.