生长促进活性的决定因素存在于胰岛素样生长因子I的A结构域中。

Determinants of growth-promoting activity reside in the A-domain of insulin-like growth factor I.

作者信息

Chen Z Z, Schwartz G P, Zong L, Burke G T, Chanley J D, Katsoyannis P G

机构信息

Department of Biochemistry, Mount Sinai School of Medicine, City University of New York, New York 10029.

出版信息

Biochemistry. 1988 Aug 9;27(16):6105-11. doi: 10.1021/bi00416a041.

DOI:10.1021/bi00416a041

PMID:3056519

Abstract

A two-chain, disulfide linked, insulin-like compound embodying the A-domain of insulin-like growth factor I (IGF-I) and the B-chain of insulin has been synthesized and characterized with respect to insulin-like biological activity and growth-promoting potency. The compound displays a potency of ca. 41% relative to insulin in assays for insulin-like activity (e.g., lipogenesis) but significantly higher activity than insulin, ca. 730% relative to insulin, in growth factor assays (e.g., thymidine incorporation). The compound is, however, a less potent growth factor than IGF-I itself, ca. 26.5% relative to IGF-I, and is not recognized by IGF carrier proteins. We conclude that structural features contained in the A-domain of IGF-I are primarily responsible for the growth-promoting ability displayed by IGF-I, while features in the B-domain are responsible for recognition by IGF carrier proteins.

摘要

一种由两条链通过二硫键连接的、类似胰岛素的化合物已被合成，该化合物包含胰岛素样生长因子I（IGF-I）的A结构域和胰岛素的B链，并已就其胰岛素样生物活性和促生长效力进行了表征。在胰岛素样活性测定（如脂肪生成）中，该化合物相对于胰岛素的效力约为41%，但在生长因子测定（如胸苷掺入）中，其活性明显高于胰岛素，相对于胰岛素约为730%。然而，该化合物作为生长因子的效力低于IGF-I本身，相对于IGF-I约为26.5%，并且不被IGF载体蛋白识别。我们得出结论，IGF-I的A结构域中包含的结构特征主要负责IGF-I所显示的促生长能力，而B结构域中的特征则负责被IGF载体蛋白识别。