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MBE Advance Access published online on December 5, 2003
Molecular Biology and Evolution, doi:10.1093/molbev/msh017
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2003; all rights reserved
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Accepted September 5, 2003
© 2003 Society for Molecular Biology and Evolution

Original Articles

Identification of a Second egfr Gene in Xiphophorus Uncovers an Expansion of the Epidermal Growth Factor Receptor Family in Fish

Ana Gómez 1, Jean-Nicolas Volff 1, Ute Hornung 2, Manfred Schartl 1, and Claudia Wellbrock 1*

1 Physiological Chemistry I, Theodor Boveri Institute for Biosciences (Biocenter), University of Würzburg, Am Hubland, 97074 Würzburg, Germany
2 Physiological Chemistry I, Theodor Boveri Institute for Biosciences (Biocenter), University of Würzburg, Am Hubland, 97074 Würzburg, GERMANY

* To whom correspondence should be addressed. E-mail: claudia.wellbrock{at}icr.ac.uk.


  Abstract

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-orthologues 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 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.

Key Words: EGF receptor, gene duplication, receptor tyrosine kinase, Xiphophorus


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