MONOCLONAL-ANTIBODY ALPHA-IR-3 INHIBITS THE ABILITY OF INSULIN-LIKE GROWTH FACTOR-II TO STIMULATE A SIGNAL FROM THE TYPE-I RECEPTOR WITHOUT INHIBITING ITS BINDING

We have previously shown that the protein encoded by a human insulin-like growth factor I (IGF-I) receptor cDNA binds both IGF-I and II with high affinity. In the present studies, we show that a monoclonal antibody to the IGF-I receptor, αIR-3, inhibits the binding of IGF-I but not IGF-II to the expressed receptor in intact cells and after solubilization. Surprisingly, this monoclonal antibody inhibits the ability of both IGF-I and II to stimulate thymidine synthesis in cells with the expressed receptor. Moreover, this antibody inhibits the ability of both IGF-I and II to stimulate the kinase activity of the IGF-I receptor in intact cells. These results indicate that αIR-3 binds to the IGF-I receptor in such a way that it does not inhibit the binding of IGF-II but does inhibit the subsequent ability of the receptor to be activated to transmit a signal. © 1990.