MOLECULAR-CLONING AND EXPRESSION OF AN ADDITIONAL EPIDERMAL GROWTH-FACTOR RECEPTOR-RELATED GENE
MOLECULAR-CLONING AND EXPRESSION OF AN ADDITIONAL EPIDERMAL GROWTH-FACTOR RECEPTOR-RELATED GENE
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DOI：
10.1073/pnas.87.13.4905
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发表时间：
1990-07-01
影响因子：
11.1
通讯作者：
SHOYAB, M
中科院分区：
文献类型：
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作者：
PLOWMAN, GD;WHITNEY, GS;SHOYAB, M
表皮生长因子（EGF），转化生长因子。（TGF-. α）和双调节蛋白是结构和功能相关的生长调节蛋白。这些分泌的多肽都与170 kda细胞表面的EGF受体结合，激活其内在的激酶活性。然而，amphiregulin表现出与EGF和TGF-. α不同的活性。在一些生物分析中。双侧调节蛋白仅部分与EGF竞争结合EGF受体，且双侧调节蛋白在TGF- β存在下不诱导正常大鼠肾细胞（NRK）锚定非依赖性生长。双调节蛋白似乎也消除了TGF- α的刺激作用。过度表达EGF受体的侵袭性上皮癌的生长这些发现表明，双调节蛋白可能在某些细胞类型中与单独的受体相互作用。在这里，我们报道克隆了人类EGF受体（HER）受体酪氨酸激酶家族的另一个成员，我们将其命名为“HER3/ERRB3”。该cDNA从人癌细胞系中分离得到，并在多种人体组织中鉴定出6千碱基的转录物。我们已经生成了肽特异性抗血清，可以识别在COS细胞中瞬时表达的160 kda HER3蛋白。这些试剂将使我们能够确定HER3是否与双调节蛋白或其他生长调节蛋白结合，以及HER3蛋白在调节细胞生长中起什么作用。
Epidermal growth factor (EGF), transforming growth factor .alpha. (TGF-.alpha.), and amphiregulin are structurally and functionally related growth regulatory proteins. These secreted polypeptides all bind to the 170-kDa cell-surface EGF receptor, activating its intrinsic kinase activity, However, amphiregulin exhibits different activities than EGF and TGF-.alpha. in a number of biological assays. Amphiregulin only partially competes with EGF for binding EGF receptor, and amphiregulin does not induce anchorage-independent growth of normal rat kidney cells (NRK) in the presence of TGF-.beta.. Amphiregulin also appears to abrogate the stimulatory effect of TGF-.alpha. on the growth of several aggressive epithelial carcinomas that overexpress EGF receptor. These findings suggest that amphiregulin may interact with a separate receptor in certain cell types. Here we report the cloning of another member of the human EGF receptor (HER) family of receptor tyrosine kinases, which we have named "HER3/ERRB3." The cDNA was isolated from a human carcinoma cell line, and its 6-kilobase transcript was identified in various human tissues. We have generated peptide-specific antisera that recognizes the 160-kDa HER3 protein when transiently expressed in COS cells. These reagents will allow us to determine whether HER3 binds amphiregulin or other growth regulatory proteins and what role HER3 protein plays in the regulation of cell growth.