Identification of a second egfr gene in Xiphophorus uncovers an expansion of the epidermal growth factor receptor family in fish
Identification of a second egfr gene in Xiphophorus uncovers an expansion of the epidermal growth factor receptor family in fish
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DOI：
10.1093/molbev/msh017
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发表时间：
2004-02-01
影响因子：
10.7
通讯作者：
Wellbrock, C
中科院分区：
文献类型：
--
作者：
G贸mez, A;Volff, JN;Wellbrock, C
表皮生长因子受体（EGFR）是哺乳动物中由四个成员（EGFR、ErbB2、ErbB3和ErbB4）形成的受体家族的名称。这个家族的成员可以被激活成为有效的致癌基因，许多人类和动物肿瘤表达定性或定量改变的受体。我们已经分离出第二个EGFR基因的黑色素瘤模型鱼剑尾鱼的特点。剑尾鱼egfra和egfrb复制品都是哺乳动物egfr基因的同源基因。数据库分析表明，不仅egfr，而且erbB3和erbB4在某些鱼类中以重复形式存在。它们起源于古老的复制事件，这可能与鱼类特异性基因组复制的假设一致。在剑尾鱼中，egfrb基因经历了第二次复制，产生了黑色素瘤诱导癌基因Xmrk。对两种剑尾鱼EGF受体的表达谱、配体结合能力和细胞内信号转导等功能特征的研究和比较表明，剑尾鱼Egfra不仅与Egfrb和人EGFR具有共同的特征，而且在功能特征上也存在显著差异。维持这些副本的机制仍有待澄清。
The epidermal growth factor receptor (EGFR) gives name to a family of receptors formed by four members in mammals (EGFR, ErbB2, ErbB3, and ErbB4). Members of this family can be activated to become potent oncogenes, and many human and animal tumors express qualitatively or quantitatively altered receptors from this group. We have isolated and characterized a second egfr gene in the melanoma model fish Xiphophorus. Both Xiphophorus egfra and egfrb duplicates are co-orthologs of the mammalian egfr gene. Database analysis showed that not only egfr but also erbB3 and erbB4 are present as duplicates in some fish species. They originated from ancient duplication events that might be consistent with the hypothesis of a fish-specific genome duplication. In Xiphophorus, the egfrb gene underwent a second duplication that generated the melanoma-inducing oncogene Xmrk. The study and comparison of some of the functional characteristics of both Xiphophorus EGF receptors, including expression profile, ligand-binding abilities, and intracellular signal transduction revealed that Xiphophorus Egfra not only shares common features with Egfrb and the human EGFR but also shows significant differences in its functional characteristics. The mechanism of maintenance of these duplicates remains to be clarified.