Structure and expression of a chicken insulin-like growth factor I precursor.
Insulin-like growth factor I (IGF-I) is a 70 amino acid growth-promoting polypeptide whose sequence and functions have been highly conserved among mammals. As an initial step in defining the role of IGF-I in other vertebrate species, we have isolated and characterized an IGF-I cDNA from the chicken. This cDNA encodes a 153 amino acid primary translation product which resembles in structure and sequence the IGF-IA protein of mammals. There is strong amino acid conservation between chicken and mammalian IGF-I throughout the entire protein. Sixty of 70 amino acids are identical in mature IGF-I among the chicken, rat, and human peptides, with five differences being localized to the C domain, and two to the D region. A comparable degree of amino acid identity is found in the COOH-terminal extension peptide (28/35 residues). At the NH2-terminus, where there is more amino acid divergence (32/48 identities), the most 5'-AUG codon is the only methionine residue conserved among all three species, suggesting that it functions as the authentic translation initiation site, an observation supported by cell-free studies of biosynthesis and cotranslational proteolytic processing. The pattern of IGF-I gene expression appears to be simpler in chickens than in mammals, since a single predominant mRNA of 2.6 kilobases can be detected in liver polyadenylated RNA on Northern blots. In the chicken, as in rats and humans, IGF-I mRNA is synthesized in multiple tissues, including liver, brain, skeletal muscle, and heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Kajimoto
Y
Y
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Rotwein
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013002:Somatomedins / Q000235:genetics*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
D011498:Protein Precursors; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I