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

AUTOR(ES)

Kasuga, M

RESUMO

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 of this receptor by covalently crosslinking two 125I-labeled IGFs, IGF-I and multiplication-stimulating activity (MSA), to chicken embryo fibroblasts by using disuccinimidyl suberate. After solubilization, NaDodSO4/polyacrylamide gel electrophoresis, and autoradiography, IGF receptor complexes of appropriate specificity were identified; they had Mr approximately 130,000 (major band) and approximately 260,000 (minor band) under reducing conditions and Mr greater than 300,000 without disulfide reduction. The proportion of the 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 effects of the IGFs contains a Mr approximately 130,000 binding subunit and exists as a native receptor complex of Mr greater than 300,000.

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