Transforming growth factor-beta modulates the high-affinity receptors for epidermal growth factor and transforming growth factor-alpha.
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-alpha to induce the transformed phenotype in NRK cells is greatly potentiated by TGF-beta, a polypeptide that does not interact directly with binding sites for EGF or TGF-alpha. Our evidence indicates that TGF-beta purified from retrovirally transformed rat embryo cells and human platelets induces a rapid (t 1/2 = 0.3 h) decrease in the binding of EGF and TGF-alpha to high-affinity cell surface receptors in NRK cells. No change due to TGF-beta was observed in the binding of EGF or TGF-alpha to lower affinity sites also present in NRK cells. The effect of TGF-beta on EGF/TGF-alpha receptors was observed at concentrations (0.5-20 pM) similar to those at which TGF-beta 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-alpha and 125I-EGF indicated that both factors interact with a common 170-kD receptor structure. Treatment of cells with TGF-beta decreased the intensity of affinity-labeling of this receptor structure. These data suggest that the 170 kD high-affinity receptors for EGF and TGF-alpha in NRK cells are a target for rapid modulation by TGF-beta.
Massagué
J
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D000818:Animals; D001667:Binding, Competitive; D001792:Blood Platelets; D002478:Cells, Cultured; D066246:ErbB Receptors; D007668:Kidney; D008970:Molecular Weight; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D015291:Transforming Growth Factors
D010455:Peptides; D011956:Receptors, Cell Surface; D015291:Transforming Growth Factors; D066246:ErbB Receptors