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An antibody that blocks insulin-like growth factor (IGF) binding to the type II IGF receptor is neither an agonist nor an inhibitor of IGF-stimulated biologic responses in L6 myoblasts.

1987; Elsevier BV; Volume: 262; Issue: 26 Linguagem: Inglês

10.1016/s0021-9258(18)45269-6

1083-351X

Wieland Kieß, Joyce F. Haskell, L Lee, Lawrence A. Greenstein, Bonnie E. Miller, A L Aarons, Matthew M. Rechler, S. Peter Nissley,

Metabolism, Diabetes, and Cancer

To better define the biologic function of the type I1 insulin-like growth factor (IGF) receptor, we raised a blocking antiserum in a rabbit by immunizing with highly purified rat type I1 IGF receptor.On immunoblots of crude type I1 receptor preparations, only bands corresponding to the type I1 IGF receptor were seen with IgG 3637, indicating that the antiserum was specific for the type I1 receptor.Competitive binding and chemical cross-linking experiments showed that IgG 3637 blocked binding of 12SI-IGF-II to the rat type I1 IGF receptor, but did not block binding of lZ6I-IGF-I to the type I IGF receptor, nor did IgG 3637 block binding of 12sI-insulin to the insulin receptor.In addition, IgG 3637 did not inhibit the binding of '2SI-IGF-II to partially purified 150-and 40-kDa IGF carrier proteins from adult and fetal rat serum.L6 myoblasts have both type I and type I1 IGF receptors.IGF-I was more potent than IGF-I1 in stimulating N-methyl-a-['4C]aminoisobutyric acid uptake, 2-r3H] deoxyglucose uptake, and [3H]leucine incorporation into cellular proteins.IgG 3637 did not stimulate either 2-[3H]deoxyglucose uptake, N-methyl-a-["C] aminoisobutyric acid uptake, or [3H]leucine incorporation into protein when tested alone.Furthermore, IgG 3637 at concentrations sufficient to block type I1 receptors under conditions of the uptake and incorporation experiments did not cause a shift to the right of the dose-response curve for stimulation of these biologic functions by IGF-11.We conclude that the type I1 IGF receptor does not mediate IGF stimulation of Nmethyl-a-['4C]aminoisobutyric acid and 2-[3H]deoxyglucose uptake and protein synthesis in L6 myoblasts; presumably, the type I receptor mediates these biologic responses.The anti-type 11 receptor antibody inhibited IGF-I1 degradation in the media by greater than 90%, suggesting that the major degradative pathway for IGF-I1 in L6 myoblasts utilizes the type I1 IGF receptor.