Immunological similarity between the insulin receptor and the protein encoded by the src oncogene.
Insulin receptors resemble receptors for certain growth factors (epidermal growth factor, platelet-derived growth factor, and insulin-like growth factor I) in that all possess tyrosine-specific protein kinase activity. These cell surface receptors resemble protein kinases encoded by viral oncogenes in that both groups of enzymes phosphorylate proteins on tyrosine. Recently, we reported that there is immunological similarity between the insulin receptor and pp60src [the protein encoded by the src oncogene of Rous sarcoma virus (RSV)]. This is supported by the observation that anti-pp60src antiserum (TBR serum) immunoprecipitated radiolabeled insulin receptors derived from cultured human cells (IM-9 lymphoblasts and U-937 monocytes) and rabbit liver. Moreover, highly purified preparations of src protein inhibit the immunoprecipitation of insulin receptors by TBR serum, and the inhibition is correlated with the src kinase activity present in the preparation used. However, two observations suggested that there were immunological differences between pp60src and mammalian insulin receptors. 1) Even at a relatively high concentration (dilution, 1:10), TBR serum immunoprecipitated a relatively small percentage (approximately 20%) of the labeled insulin receptors. 2) Some lots of TBR serum with a high titer against pp60src failed to immunoprecipitate the insulin receptor. Viral oncogenes are thought to have been derived from proto-oncogenes in the host cell. Therefore, because the chicken is the natural host for RSV, we inquired whether there might be closer homology between pp60src and avian insulin receptors. Surprisingly, under conditions where TBR serum immunoprecipitates human insulin receptors, we could not detect immunoprecipitation of avian insulin receptors from chicken liver, chicken embryo fibroblasts, or turkey erythrocytes. The immunoprecipitation of human insulin receptor is not dependent on the method used for labeling the cells ([125I]insulin cross-linking), inasmuch as the receptor labeled by autophosphorylation with [gamma-32P]ATP could also be immunoprecipitated by TBR serum. These observations suggest that there is structural homology between pp60src and the insulin receptor (most likely the beta-subunit). Nevertheless, it seems unlikely that the insulin receptor gene is the proto-oncogene for the src gene of RSV.
D000818:Animals; D000941:Antigens / Q000276:immunology; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens; D005347:Fibroblasts / Q000032:analysis; D006801:Humans; D007163:Immunosorbent Techniques; D008214:Lymphocytes / Q000032:analysis; D008862:Microsomes, Liver / Q000032:analysis; D009000:Monocytes / Q000032:analysis; D015688:Oncogene Protein pp60(v-src); D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D000090063:Proto-Oncogene Mas; D011817:Rabbits; D011972:Receptor, Insulin / Q000235:genetics / Q000276:immunology*; D012191:Retroviridae Proteins / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity
D000941:Antigens; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012191:Retroviridae Proteins; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D015688:Oncogene Protein pp60(v-src)