Antireceptor antibodies as probes of insulinlike growth factor receptor structure.
Insulin receptors and Type I insulinlike growth factor (IGF) receptors have a similar structure with a major binding subunit of Mr approximately 130,000 linked by disulfide bonds to other membrane proteins to form a Mr greater than 300,000 complex. Both insulin and Type I IGF receptors also interact with both insulin and IGF, although with different binding affinities. We used a panel of human and rabbit sera containing antibodies to insulin receptors to determine whether these sera also interact with Type I IGF receptors. Immunoglobulins from five of five human sera inhibited binding of 125I-insulin and 125I-IGF-I to insulin receptors and Type I IGF receptors in human placenta and human lymphocytes. The rank order of reactivity with both receptors was the same; two sera, however, appeared to be selectively less reactive with the Type I IGF receptor, especially in placenta. Sera from five of seven patients and from a rabbit immunized with purified insulin receptor effectively immunoprecipitated both placental insulin receptors and Type I IGF receptors. Of the remaining sera, one had only a low titer against the insulin receptor and did not immunoprecipitate the IGF receptor, whereas the second serum effectively immunoprecipitated cross-linked and surface-iodinated insulin receptors, but had negligible reactivity against the Type I IGF receptor. These results suggest that most antisera to the insulin receptor also contain antibodies to Type I IGF receptors. Whether both specificities are inherent in the same or different antibody molecules remains to be determined. These data support the hypothesis that the insulin and IGF-I receptors are separate but related molecules, although there remains a small possibility that both receptors are domains on the same protein.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000032:analysis; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000502:physiology*; D001667:Binding, Competitive; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006801:Humans; D008099:Liver; D008214:Lymphocytes / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D010920:Placenta; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D011972:Receptor, Insulin; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000276:immunology; D017451:Receptors, Somatomedin
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D011972:Receptor, Insulin