Phylogeny of the insulin-like growth factors (IGFs) and receptors: a molecular approach.
The IGFs (IGF-I and IGF-II) are essential for normal mammalian growth and development. Their actions are mediated primarily by their interactions with the type I IGF receptor (IGF-I receptor), a transmembrane tyrosine kinase. The ligands and the IGF-I receptor are structurally related to insulin and to the insulin receptor, respectively. Analysis of 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 550 million years. The insulin receptor is also highly conserved in vertebrate species, and an insulin-receptor-like molecule has been characterized in Drosophila. In contrast, IGF-I receptors have only been characterized in mammalian species and partially studied in Xenopus, in which the tyrosine kinase domain is highly conserved. Studies are presently being undertaken to analyze in more detail the regulation of the genes encoding this important family of growth factors and the structure/function relationships in the gene products themselves.
Section on Molecular and Cellular Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
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D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D015870:Gene Expression; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017526:Receptor, IGF Type 1 / Q000737:chemistry / Q000235:genetics*; D017527:Receptor, IGF Type 2 / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1