Determinants of growth-promoting activity reside in the A-domain of insulin-like growth factor I |
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| Authors: | Z Z Chen G P Schwartz L Zong G T Burke J D Chanley P G Katsoyannis |
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| Affiliation: | Department of Biochemistry, Mount Sinai School of Medicine, City University of New York, New York 10029. |
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| 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. |
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