Cell-type specific interaction of Neu differentiation factor (NDF/heregulin) with Neu/HER-2 suggests complex ligand-receptor relationships.

Research Article1 March 1993free access Cell-type specific interaction of Neu differentiation factor (NDF/heregulin) with Neu/HER-2 suggests complex ligand-receptor relationships. E. Peles E. Peles Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author R. Ben-Levy R. Ben-Levy Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author E. Tzahar E. Tzahar Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author N. Liu N. Liu Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author D. Wen D. Wen Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author Y. Yarden Y. Yarden Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author E. Peles E. Peles Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author R. Ben-Levy R. Ben-Levy Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author E. Tzahar E. Tzahar Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author N. Liu N. Liu Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author D. Wen D. Wen Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author Y. Yarden Y. Yarden Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. Search for more papers by this author Author Information E. Peles1, R. Ben-Levy1, E. Tzahar1, N. Liu1, D. Wen1 and Y. Yarden1 1Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel. The EMBO Journal (1993)12:961-971https://doi.org/10.1002/j.1460-2075.1993.tb05737.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info The Neu/HER-2 receptor tyrosine kinase is overexpressed in some types of human adenocarcinomas, including tumors of the breast and the ovary. A 44 kDa glycoprotein that elevates tyrosine phosphorylation of Neu has been isolated and named Neu differentiation factor (NDF), or heregulin. Here we show that NDF affects tyrosine phosphorylation of Neu in human tumor cells of breast, colon and neuronal origin, but not in ovarian cells that overexpress the receptor. By using monoclonal antibodies (mAbs) to Neu, we found that the ovarian receptor is immunologically and biochemically similar to the mammary p185neu. Nevertheless, unlike breast-derived Neu, the ovarian protein did not display covalent cross-linking to radiolabeled NDF, and was devoid of ligand-induced association with phosphatidylinositol 3′-kinase. Direct binding analysis showed that NDF binds with high affinity (Kd approximately 10(−9) M) to mammary cells, but its weak association with ovarian cells is probably mediated by heparin-like molecules. Similar to the endogenous receptor, the ectopically overexpressed Neu of mammary cells, but not of ovarian and fibroblastic cells, exhibited elevated levels of NDF-induced phosphorylation and covalent cross-linking of the radiolabeled factor. Taken together, our results imply that NDF binding to cells requires both Neu and an additional cellular component, whose identity is still unknown, but its tissue distribution is more restricted than the expression of the neu gene. Previous ArticleNext Article Volume 12Issue 31 March 1993In this issue RelatedDetailsLoading ...