Determinants of growth-promoting activity reside in the A-domain of insulin-like growth factor I.
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.
Chen
Z Z
ZZ
Department of Biochemistry, Mount Sinai School of Medicine, City University of New York, New York 10029.
Schwartz
G P
GP
Zong
L
L
Burke
G T
GT
Chanley
J D
JD
Katsoyannis
P G
PG
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000138:chemical synthesis / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008934:Mitogens; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D013002:Somatomedins / Q000494:pharmacology*
D007328:Insulin; D008055:Lipids; D008934:Mitogens; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin