The Structural and Biological Properties of Heparin-Binding Egf- Like Growth Factor (HB-EGF)

Abstract

The epidermal growth factor (EGF) protein family encompasses a number of structurally homologous mitogens including EGF, transforming growth factor-α (TGF-α), vaccinia growth factor (VGF), amphiregulin (AR), heparin-binding EGF-like growth factor (HB- EGF) and heregulin/Neu differentiation factor (HRG/NDF) (Carpenter and Wahl, 1990; Derynck et al., 1985; Brown et al., 1985; Shoyab et al., 1989; Higashiyama et al., 1991; Wen et al., 1992; Holmes et al., 1992). HB-EGF was originally identified in our laboratory in the conditioned medium of human monocytes, macrophages and the macrophage-like cell line, U-937. It was named heparin-binding EGF-like growth factor because of its strong affinity for immobilized heparin (elution with 1.0–1.2 M NaCl), a property not shared by EGF or TGF-α. It is speculated that the heparin-binding properties of HB-EGF may be of biological significance. In recent years, a growing number of heparin-binding growth factors have been identified. Some examples are members of the fibroblast growth factor (FGF) family, platelet-derived growth factor (PDGF), and vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) (see review; Klagsbrun, 1992). Interaction with cell surface heparan sulfate proteoglycan has been demonstrated to facilitate the binding of basic FGF (bFGF) to its high affinity receptor and to enhance mitogenic activity. (Yayon et al., 1991; Rapraeger et al., 1991; Klagsbrun and Baird, 1991; Ornitz et al., 1992). We speculate that the ability of HB-EGF to bind to cell surface heparan sulfate proteoglycan might also modulate its biological activity.