表皮生长因子受体2（ErbB-2）受体酪氨酸激酶的催化活性对胚胎发育至关重要。
The catalytic activity of the ErbB-2 receptor tyrosine kinase is essential for embryonic development.
作者信息
Chan Richard, Hardy William R, Laing Michael A, Hardy Sarah E, Muller William J
机构信息
Department of Biology, McMaster University, Hamilton, Ontario, Canada L8S 4K1.
出版信息
Mol Cell Biol. 2002 Feb;22(4):1073-8. doi: 10.1128/MCB.22.4.1073-1078.2002.
Abstract
Activation of the epidermal growth factor receptor (EGFR) family is thought to play a critical role in both embryogenesis and oncogenesis. The diverse biological activities of the EGFR family are achieved through various ligand-receptor and receptor-receptor interactions. One receptor that has been found to play a central role in this signaling network is ErbB-2/Neu, and it is considered the preferred heterodimerization partner for other members of the EGFR family. To assess the importance of the catalytic activity of ErbB-2 in embryonic development, we have generated mice expressing a kinase-dead erbB-2 cDNA under the transcriptional control of the endogenous promoter. Here, we show that mice homozygous for the kinase-dead erbB-2 allele die at midgestation and display the same spectrum of embryonic defects seen in erbB-2 knockout mutants. These observations suggest that the catalytic activity of ErbB-2 is essential for normal embryonic development.
摘要
表皮生长因子受体（EGFR）家族的激活被认为在胚胎发育和肿瘤发生过程中都起着关键作用。EGFR家族多样的生物学活性是通过各种配体-受体以及受体-受体相互作用来实现的。已发现一种在该信号网络中起核心作用的受体是ErbB-2/Neu，它被认为是EGFR家族其他成员的首选异源二聚化伴侣。为了评估ErbB-2的催化活性在胚胎发育中的重要性，我们构建了在内源启动子转录控制下表达激酶失活型erbB-2 cDNA的小鼠。在此，我们表明激酶失活型erbB-2等位基因纯合的小鼠在妊娠中期死亡，并表现出与erbB-2基因敲除突变体相同的一系列胚胎缺陷。这些观察结果表明，ErbB-2的催化活性对于正常胚胎发育至关重要。
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