Sequence of cDNA encoding human insulin-like growth factor I precursor

Abstract

Somatomedins (SM) or insulin-like growth factors (IGF) constitute a heterogeneous group of peptides1 with important growth-promoting effects in vitro2,3 as well as in vivo4,5. Amino acid sequences have been determined for only two of them, IGF-I and IGF-II, which are highly homologous6,7. IGF-I, which is identical with SM-C8, is composed of 70 amino acid residues and IGF-II contains 73 amino acids and may be identical with SM-A9. Other peptides with different charge properties but with similar SM-like or insulin-like behaviour in biological and receptor assays, have been described but have not yet been fully characterized1. The liver is known to be a major site of production of these peptides10, but many other tissues—especially in the fetus11—may synthesize them as well. We report here the nucleotide sequence of a human liver cDNA encoding the complete amino acid sequence of IGF-I. The IGF-I coding region is flanked by sequences encoding an amino-terminal peptide of at least 25 amino acid residues and a carboxyl-terminal peptide of 35 amino acids. This provides evidence that IGF-I is synthesized as a precursor protein and that formation of IGF-I from this precursor requires proteolytic processing at both ends.