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.
Verland
S
S
Department of Clinical Chemistry, Bispebjerg Hospital, Copenhagen, Denmark.
Gammeltoft
S
S
D000345:Affinity Labels; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013945:Thymoma / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000378:metabolism*
D000345:Affinity Labels; D000596:Amino Acids; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D003208:Concanavalin A; D011505:Protein-Tyrosine Kinases