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, alpha IR-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 alpha IR-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.
Steele-Perkins
G
G
Department of Pharmacology, Stanford University School of Medicine, CA 94305.
Roth
R A
RA
D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D002460:Cell Line; D004789:Enzyme Activation; D007335:Insulin-Like Growth Factor II / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D007335:Insulin-Like Growth Factor II