Isolation of a cDNA clone encoding rat insulin-like growth factor-II precursor

• Published in: Nature (London) 1984-11, Vol.312 (5991), p.277-280
• Main Authors: Whitfield, Harvey J., Bruni, Carmelo B., Frunzio, Rodolfo, Terrell, Jeffrey E., Nissley, S. Peter, Rechler, Matthew M.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Biotechnology; Cloning, Molecular; DNA - genetics; Fundamental and applied biological sciences. Psychology; Genes. Genome; Genetic engineering; Genetic technics; Growth Substances - genetics; Humanities and Social Sciences; Insulin - genetics; letter; Methods. Procedures. Technologies; Molecular and cellular biology; Molecular cloning; Molecular genetics; Molecular Weight; multidisciplinary; Peptides - genetics; Protein Precursors - genetics; Rats; RNA, Messenger - genetics; Science; Science (multidisciplinary); Somatomedins - genetics
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/312277a0

Insulin-like growth factor-I (IGF-I) and IGF-II are mitogenic polypeptides of relative molecular mass ( M r ) ∼7,500 isolated from human plasma 1,2 each containing four peptide domains in a single chain and identical at more than 60% of their amino acid loci. The B- and A-domains of the IGFs are ∼40% identical to the B-and A-chains of human insulin 1,2 . IGF-I and IGF-II have similar in vitro biological activities 2 and receptor reactivity 3 , but are immunologically distinct 4,5 . IGF-I appears to mediate the effects of growth hormone on cartilage to promote skeletal growth 5,6 , whereas IGF-II may have a special role in fetal development 7,8 and in the central nervous system 9 . To investigate the in vivo role of IGF-II, we have studied IGF-II biosynthesis in the BRL-3A rat liver cell line 10 . BRL-3A cells synthesize and secrete a 7,484 M r protein 93% identical to human IGF-II and representing rat IGF-II (rIGF-II) 11 . Rat IGF-II is synthesized as a ∼22,000 M r prepro-rIGF-II (ref. 12) from 12 S poly(A) + mRNA 13 . In addition, ∼20,000 M r pro-rIGF-II has been identified in lysates of biosynthetically labelled intact BRL-3A cells 14 . We report here the isolation of an almost complete cDNA clone for rIGF-II. Our results indicate that pro-rIGF-II is synthesized as a 156 amino acid peptide precursor (17,619 M r ) containing mature rIGF-II 1–67 at its amino-terminus and an 89-residue carboxy-terminal peptide extension.