Human Insulin-Like Growth Factor-I And Factor-Ii (Igf-I, Igf-Ii) Are Synthesized As Precursors

In an attempt to further investigate the structure of the Somatomedins/Insulin-like Growth Factors (SM/IGF), especially the possible existence of precursor peptides and their structural relation to the circulating forms, we have used recombinant-DNA techniques to identify and isolate cDNA-clones encoding human IGF-I and -II. By screening an adult human liver cDNA-library with a synthetic oligonucleotide, we initially isolated a cDNA encoding the 70 amino acids of IGF-I preceded by an N-terminal peptide of at least 25 amino acids and a carboxyl-terminal peptide of 35 amino acids, thus demonstrating that IGF-I is synthesized as a precursor. Subsequently, by cross-hybridizing the cDNA-library with restriction fragments of this cDNA we were able to isolate another cDNA clone, encoding the 67 amino acids of IGF-II, flanked by nucleotide sequences encoding a highly hydrophobic leader peptide and a carboxyl-terminal peptide. These results provide solid evidence that both IGF-I and IGF-II are synthesized as precursor proteins and that formation of IGF-I and IGF-II from these precursors requires proteolytic processing at both the N-terminal and the C-terminal ends.