Biosynthesis of human insulin-like growth factor I (IGF-I). The primary translation product of IGF-I mRNA contains an unusual 48-amino acid signal peptide.
The human insulin-like growth factor I (IGF-I) gene can specify two primary translation products, IGF-IA and IGF-IB, which differ at their COOH termini and which must undergo extensive proteolytic processing to produce the mature 70-residue circulating peptide. We have used an in vitro transcription/translation/microsomal membrane processing system to define the early events in IGF-I biosynthesis. Our results demonstrate that protein synthesis is initiated at the first in-frame methionine codon for both human IGF-IA and IGF-IB mRNAs, yielding primary translation products of 153 and 195 residues, respectively. Both are cotranslationally translocated into the lumen of canine pancreatic microsomes. Cotranslational proteolytic processing results in the removal of an unusually large 48-amino acid signal peptide. Computer-assisted sequence analysis revealed that this prepeptide contains two domains. Its COOH-terminal 19 residues possess features which are typically encountered in eukaryotic signal peptides. The rest of the IGF-I signal sequence is represented by an unusual "extended" NH2-terminal domain containing an overall net charge of +5 and 3 clustered cysteines. The size and charge of this NH2-terminal domain distinguish it from comparable regions of other eukaryotic signal peptides including the presegment of human IGF-II. Although no specialized biological role can currently be ascribed to this unique NH2-terminal domain, its remarkable sequence conservation between human and rat suggests an as yet unknown functional significance.
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D001330:Electronic Data Processing; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013002:Somatomedins / Q000096:biosynthesis* / Q000235:genetics
D021382:Protein Sorting Signals; D012333:RNA, Messenger; D013002:Somatomedins; D004247:DNA; D008715:Methionine; D007930:Leucine