Binding specificities and affinities of egf domains for ErbB receptors

ErbB receptor activation is a complex process and is dependent upon the typ e and number of receptors expressed on a given cell, Previous studies with defined combinations of ErbB receptors expressed in mammalian cells have he lped elucidate specific biological responses for many of the recognized gen e products that serve as ligands for these receptors, However, no study has examined the binding of these ligands in a defined experimental system. To address this issue, the relative binding affinities of the egf domains of eleven ErbB ligands were measured on six ErbB receptor combinations using a soluble receptor-ligand binding format. The ErbB2/4 heterodimer was shown to hind all ligands tested with moderate to very high affinity. In contrast , ErbB3 showed much more restrictive ligand binding specificity and measura ble binding was observed only with heregulin, neuregulin2 beta, epiregulin and the synthetic heregulin/egf chimera, biregulin, These studies also reve aled that ErbB2 preferentially enhances ligand binding to ErbB3 or ErbB4 an d to a lesser degree to ErbB1. (C) 1999 Federation of European Biochemical Societies.