Insulin-like growth factor II precursor gene organization in relation to insulin gene family

Abstract

The insulin gene family^1,2, comprised of insulin, relaxin, insulin-like growth factors I and II (IGF-I and IGF-II) and possibly the β-subunit of 7S nerve growth factor³, represents a group of structurally related polypeptides whose biological functions have diverged. The IGFs, or somatomedins, constitute a class of polypeptides that have a key role in pre-adolescent mammalian growth (see ref. 4 for review). IGF-I expression is regulated by growth hormone^5,6 and mediates postnatal growth, while IGF-II appears to be induced by placental lactogen during prenatal development⁶. The primary structures of both human IGFs have been determined and are closely related^7,8. A polypeptide highly homologous to human IGF-II is secreted by the rat liver cell line, BRL-3A^9,10. As this polypeptide, termed multiplication stimulating activity (MSA), differs from human IGF-II by only five amino acid residues, MSA probably represents the rat IGF-II protein¹¹. Using molecular cloning techniques, we have isolated cDNA and chromosomal genes coding for the MSA and human IGF-II precursors, respectively. Our data, presented here, indicate that both MSA¹² and human IGF-II are synthesized initially as larger precursor molecules. The deduced preprohormones both have molecular weights (MWs) of 20,100 and contain C-terminal propeptides of 89 amino acid residues, which we have named E-peptides. The organization of the IGF-II precursor gene is discussed in relation to that of other insulin gene family members.