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

摘要: The Neu/HER-2 receptor tyrosine kinase is overexpressed in some types of human adenocarcinomas, including tumors the breast and ovary. A 44 kDa glycoprotein that elevates phosphorylation Neu has been isolated named differentiation factor (NDF), or heregulin. Here we show NDF affects tumor cells breast, colon neuronal origin, but not ovarian overexpress receptor. By using monoclonal antibodies (mAbs) to Neu, found immunologically biochemically similar mammary p185neu. Nevertheless, unlike breast-derived protein did display covalent cross-linking radiolabeled NDF, was devoid ligand-induced association with phosphatidylinositol 3'-kinase. Direct binding analysis showed binds high affinity (Kd approximately 10(-9) M) cells, its weak probably mediated by heparin-like molecules. Similar endogenous receptor, ectopically fibroblastic exhibited elevated levels NDF-induced factor. Taken together, our results imply requires both an additional cellular component, whose identity still unknown, tissue distribution more restricted than expression neu gene.