PHYLOGENY OF THE INSULIN-LIKE GROWTH-FACTORS (IGFS) AND RECEPTORS - AMOLECULAR APPROACH

The IGFs (IGF-I and IGF-II) are essential for normal mammalian growth and development. Their actions are mediated primarily by their interac tions with the type I IGF receptor (IGF-I receptor), a transmembrane t yrosine kinase. The ligands and the IGF-I receptor are structurally re lated to insulin and to the insulin receptor, respectively. Analysis o f evolutionary conservation has often provided insights into essential regions of molecules such as hormones and their receptors. The genes for insulin and IGFs have been partially characterized in a number of vertebrate species extending evolutionarily from humans as far back as fish. The sequences of the exons encoding the mature insulin and IGF peptides are highly conserved among vertebrate species, and IGF-I-like molecules are found in species whose origins extend back as much as 5 50 million years. The insulin receptor is also highly conserved in ver tebrate species, and an insulin-receptor-like molecule has been charac terized in Drosophila. In contrast, IGF-I receptors have only been cha racterized in mammalian species and partially studied in Xenopus, in w hich the tyrosine kinase domain is highly conserved. Studies are prese ntly being undertaken to analyze in more detail the regulation of the genes encoding this important family of growth factors and the structu re/function relationships in the gene products themselves. (C) 1993 Wi ley-Liss, Inc.