Functional receptors for insulin-like growth factors I and II in rat thymocytes and mouse thymoma cells

Functional receptors for insulin-like growth factors (IGF) I and II have been identified in rat thymocytes and mouse thymoma cell lines R1.1 and S49.1. IGF-I receptor alpha-subunit (MW 130,000) bind IGF-I and IGF-II with equal affinity (Kd approximately 4-7 nM), and insulin with approximately 100 times lower affinity. Tyrosine kinase activity and autophosphorylation of the IGF-I receptor beta-subunit (MW 95,000) are stimulated by IGF-I and IGF-II with equal potency (ED50 approximately 0.5 nM). IGF-II receptors (MW 250,000) bind IGF-II with Kd approximately 0.3 nM and IGF-I with 30 times lower affinity, but not insulin. IGF-I and IGF-II do not cross-react with the insulin receptor to which insulin binds with an apparent Kd approximately 1 nM, and stimulates its tyrosine kinase activity with ED50 approximately 3 nM. In thymocytes, alpha-aminoisobutyric acid transport is stimulated 2-fold by IGF-I and IGF-II with identical potency (ED50 approximately 2 nM), and by insulin with ED50 approximately 10 nM. Activation of thymocytes by concanavalin A increased the number of IGF-II receptors 2-fold, whereas IGF-I receptor binding and IGF-stimulated amino acid transport were unaltered. We conclude that the effect of IGF-I and IGF-II in thymocytes is mediated via binding to the IGF-I receptor and stimulation of its tyrosine kinase. The presence of functional IGF receptors on thymocytes and thymoma cells suggests that IGF-I and IGF-II play a role in the regulation of thymic functions.