Transforming growth factor-β modulates the high-affinity receptors for epidermal growth factor and transforming growth factor-α

Abstract

The epidermal growth factor (EGF) receptor mediates the induction of a transformed phenotype in normal rat kidney (NRK) cells by transforming growth factors (TGFs). The ability of EGF and its analogue TGF-α to induce the transformed phenotype in NRK cells is greatly potentiated by TGF-β, a polypeptide that does not interact directly with binding sites for EGF or TGF-α. Our evidence indicates that TGF-β purified from retrovirally transformed rat embryo cells and human platelets induces a rapid (t1/2 = 0.3 h) decrease in the binding of EGF and TGF-α to high-affinity cell surface receptors in NRK cells. No change due to TGF-β was observed in the binding of EGF or TGF-α to lower affinity sites also present in NRK cells. The effect of TGF-β on EGF/TGF-α receptors was observed at concentrations (0.5-20 pM) similar to those at which TGF-β is active in promoting proliferation of NRK cells in monolayer culture and semisolid medium. Affinity labeling of NRK cells and membranes by cross-linking with receptor-bound 125I-TGF-α and 125I-EGF indicated that both factors interact with a common 170-kD receptor structure. Treatment of cells with TGF-β decreased the intensity of affinity-labeling of this receptor structure. These data suggest that the 170 kD high-affinity receptors for EGF and TGF-α in NRK cells are a target for rapid modulation by TGF-β. © 1985, Rockefeller University Press., All rights reserved.