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Evolution of Insulin-Like Growth Factor I (IGF-I): Structure and Expression of an IGF-I Precursor from Xenopus laevis

Department of Medicine, Metabolism Division and Department of Genetics, Washington University School of Medicine St. Louis, Missouri 63110

Address requests for reprints to: Dr. Peter Rotwein, Washington University School of Medicine, Box 8127, 660 South Euclid Avenue, St. Louis, Missouri 63110.

Abstract

By means of a cloning strategy employing the polymerase chain reaction, we have isolated and characterized cDNAs for Xenopus laevis insulin-like growth factor I (IGF-I). These cDNAs encode a primary IGFI translation product of 153 residues that demonstrates considerable amino acid sequence similarity with IGF-IA peptides from other species. Fifty-seven of 70 residues of the mature protein are identical among human, rat, chicken, and Xenopus IGF-I, while less amino acid conservation is found at the COOH-terminus (25/35 identities) or at the NH₂-terminus (24/48 identities) of the precursor protein. Despite the lower degree of structural similarity at the NH₂-terminus, in vitro studies of IGF-I biosynthesis and proteolytic processing support a conserved function for the atypically long 48 residue NH₂-terminal signal sequence in directing the nascent IGF-I peptide through the secretory pathway. The 5'-untranslated region of Xenopus IGF-I mRNA matches the human, rat, and chicken sequences in greater than 90% of 279 nucleotides. IGF-I mRNAs from all four species encode a conserved upstream open reading frame of 14 amino acids starting 240-250 nucleotides 5' to the translation start site, suggesting a possible role for this region in modulating IGF-I gene expression. The X. laevis IGF-I gene is transcribed and processed into three mRNAs of 1.6, 2.1, and 3.0 kilobases in liver, and IGF-I mRNAs can be detected in liver, lung, heart, kidney, and peritoneal fat of adult animals. These studies demonstrate that both the IGF-I protein precursor and potential regulatory regions of IGF-I mRNA have been conserved during vertebrate evolution, and indicate that like several other polypeptide growth factors, IGF-I may be of fundamental importance in regulating specific aspects of growth and development in all vertebrates.

FOOTNOTES

This work was funded in part by NIH Grant DK-37449 (to P.R.).

The nucleotide sequence data reported in this paper will appear in the EMBL, Gen Bank, and DDBJ Nucleotide Sequence Databases under the accession number M29857.

Received for publication October 6, 1989. Revision received November 7, 1989. Accepted for publication November 7, 1989.

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