Interactions of insulin-like growth factors I and II and multiplication-stimulating activity with receptors and serum carrier proteins.

Insulin-like growth factors (IGFs) I and II, purified from human plasma, and multiplication-stimulating activity (MSA), purified from media conditioned by the BRL 3A rat liver cell line, are polypeptides with similar biological and biochemical properties. We have compared the interaction of 125I-labeled and unlabeled MSA, IGF-I, and IGF-II with four intact cell or cell membrane preparations previously shown to possess MSA receptors: rat liver plasma membranes, chick embryo fibroblasts, human fibroblasts, and BRL 3A2 cells. In each case, specific binding of 125I-labeled IGF-I and IGF-II was demonstrated. With each 125I-labeled peptide, significant inhibition of binding and parallel dose-response curves were observed with unlabeled IGF-I, IGF-II, and MSA. Striking differences were noted, however, in the relative potencies of the unlabeled peptides as competitive inhibitors of binding. We conclude that the different specificities of binding inhibition reflect a significant heterogeneity among IGF receptors. A similar heterogeneity appears to occur among somatomedin carrier proteins in rat and human sera.