Structure of the insulin-like growth factor receptor in chicken embryo fibroblasts.

Abstract

The insulin-like growth factors (IGFs) and insulin stimulate DNA synthesis and cell multiplication in chicken embryo fibroblasts in culture. This response appears to be mediated by interaction with a single type of IGF receptor. The present study examines the subunit structure ofthis receptor by covalently crosslinking two "MI-labeled IGFs, IGF-I and multiplication-stimulating activity (MSA), to chicken embryo fibroblasts by using disuccinimidyl suberate. After solubilization, NaDodSO4polyacryl-amide gel electrophoresis, and autoradiography, IGF receptor complexes of appropriate specificity were identified; they had Mr :130,000 (major band) and -260,000 (minor band) under reducing conditions and Mr >300,000 without disulfide reduction. The proportion ofthe Mr 260,000 component increased-with increasing concentration of crosslinking agent, suggesting that it was formed from smaller proteins during the crosslinking procedure. The IGF receptor in chicken embryo fibroblasts resembles the insulin receptor in size and structure but can be. distinguished by a higher affinity for IGF-I and MSA than for insulin. Although IGF receptors with different structure and specificity have been recognized in other tissues, the function of these binding sites is unknown. The present study demonstrates that the IGF receptor of chicken embryo fibroblasts that appears to mediate the growth-promoting

Characterization and regulation of somatomedin‐C/insulin‐like growth factor I (Sm‐C/IGF‐I) receptors on cultured pig Leydig cells

“…2). Under reducing conditions 1251-Sm-C was cross-linked predominantly to a receptor complex with apparent M , E 120000, similar to the subunit of the Sm-C receptor observed in other studies [32,331. Unlabeled Sm-C/lGF-I (200 ng/ml) inhibited the affinity labeling of Sm-C/IGF-I receptor, whereas unlabeled insulin had no effect on this band at identical concentrations.…”

Modulation of insulinlike growth factor I binding to human fibroblast monolayer cultures by insulinlike growth factor carrier proteins released to the incubation media.

“…It has been more difficult to resolve whether these effects are mediated by type I, type II, or both receptors. Some cells (e.g., chick embryo fibroblasts) only possess type I IGF receptors (2,8), so it is quite likely that in these cells the type I receptor mediates IGF-stimulated DNA synthesis. Whether the type II receptor mediates the same or different functions as the type I receptor, or indeed whether it possesses any biological functions (9) (2,(12)(13)(14).…”

Insulin activates the appearance of insulin-like growth factor II receptors on the adipocyte cell surface.

“…A receptor for IGF-II, distinct from the insulin and IGF-I receptors, has been demonstrated in a variety of tissues (4) and has been identified on electrophoretic gels by affinity crosslinking methods (5)(6)(7). The (8)(9)(10).…”