Epidermal growth factor and transforming growth factor .alpha. bind differently to the epidermal growth factor receptor

Abstract

Epidermal growth factor (EGF) and transforming growth factor .alpha. (TGF.alpha.) compete with each other for binding to the EGF receptor. These two growth factors have similar actions, but there are distinguishable differences in their biological activities. It has never been clear how this one receptor can mediate different responses. A monoclonal antibody to the EGF receptor (13A9) has been identified which has only small effects on the binding of EGF to the EGF receptor, but which has very large effects on the binding of TGF.alpha. to the EGF receptor; 5 .mu.g/mL antibody has been shown to totally block 0.87 .mu.M TGF.alpha. from binding to purified EGF receptor and to lower both the high- and low-affinity binding constants of TGF.alpha. binding to EGF receptor on A431 cells by about 10-fold. The 13A9 antibody causes a 2.5-fold stimulation of the tyrosine kinase activity of partially purified EGF receptor, compared to a 4.0-fold stimulation of the tyrosine kinase activity by EGF under the same conditions. The data suggest either that the antibody stabilizes a conformation of the EGF receptor which is not favorable for TGF.alpha. binding or that it blocks a part of the surface of the receptor which is necessary for TGF.alpha. binding but not EGF binding.