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Insights into the evolution of the ErbB receptor family and their ligands from sequence analysis

BioMed Central
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  • Research Article
  • Biology
  • Chemistry

Abstract ral ss BioMed CentBMC Evolutionary Biology Open AcceResearch article Insights into the evolution of the ErbB receptor family and their ligands from sequence analysis Richard A Stein*1 and James V Staros2 Address: 1Dept. of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA and 2Dept. of Biochemistry and Cell Biology, SUNY-Stony Brook, Stony Brook, NY 11794, USA, and Dept. of Biological Sciences, Vanderbilt University, Nashville, TN, 37235, USA Email: Richard A Stein* - [email protected]; James V Staros - [email protected] * Corresponding author Abstract Background: In the time since we presented the first molecular evolutionary study of the ErbB family of receptors and the EGF family of ligands, there has been a dramatic increase in genomic sequences available. We have utilized this greatly expanded data set in this study of the ErbB family of receptors and their ligands. Results: In our previous analysis we postulated that EGF family ligands could be characterized by the presence of a splice site in the coding region between the fourth and fifth cysteines of the EGF module and the placement of that module near the transmembrane domain. The recent identification of several new ligands for the ErbB receptors supports this characterization of an ErbB ligand; further, applying this characterization to available sequences suggests additional potential ligands for these receptors, the EGF modules from previously identified proteins: interphotoreceptor matrix proteoglycan-2, the alpha and beta subunit of meprin A, and mucins 3, 4, 12, and 17. The newly available sequences have caused some reorganizations of relationships among the ErbB ligand family, but they add support to the previous conclusion that three gene duplication events gave rise to the present family of four ErbB receptors among the tetrapods. Conclusion: This study provides strong support for the hypothesis that the presence of an easil

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