EGF-Urogastrone

Literature References: Related polypeptides that are both potent stimulators of cellular proliferation and inhibitors of gastric acid secretion. Urogastrone was originally detected as an antisecretory agent during experiments on human urine: J. S. Gray et al., Science 89, 489 (1939); M. H. F. Friedman et al., Proc. Soc. Exp. Biol. Med. 41, 509 (1935). Isoln: J. S. Gray et al., Endocrinology 30, 129 (1942); R. A. Gregory, J. Physiol. 129, 528 (1955). Improved procedures led to the isoln and amino acid sequence determn of two polypeptides, b-urogastrone and g-urogastrone: H. Gregory, Nature 257, 325 (1975). These two peptides contain 3 disulfide bonds and consist of 53 and 52 amino acid residues, respectively. The only difference between them is the absence of a C-terminal arginine residue in the g-peptide. Epidermal growth factor, or EGF, was isolated from submaxillary glands of male mice after first being detected during purification of a nerve growth promoting protein: S. Cohen, Proc. Natl. Acad. Sci. USA 46, 302 (1960); idem, J. Biol. Chem. 237, 1555 (1962). The primary structure of mouse EGF (mEGF) was found to be a 53 amino acid polypeptide containing 3 disulfide bonds: C. R. Savage et al., ibid. 247, 7612 (1972); 248, 7669 (1973). Sequence of an mEGF cDNA clone that predicts the synthesis of EGF as a large protein precursor of 1,168 amino acids: A. Gray et al., Nature 303, 722 (1983). mEGF causes premature eye opening and stimulation of epithelial cell tissue growth when injected daily into newborn mice: S. Cohen, loc. cit. (1962); S. Cohen, J. M. Taylor, Recent Prog. Horm. Res. 30, 533 (1974). The structural similarities between EGF and urogastrone led to experiments that established the gastric acid-inhibitory activity of mEGF and the proliferative activity of urogastrone, thus showing that both polypeptides have the same intrinsic biological activities, cf. H. Gregory, loc. cit. It has also been shown that both mEGF and urogastrone can share the same receptor sites in human tissue with almost equal affinities: M. D. Hollenberg, H. Gregory, Life Sci. 20, 267 (1976). Human EGF has been isolated from urine: S. Cohen, G. Carpenter, Proc. Natl. Acad. Sci. USA 72, 1317 (1975). The similarity of its amino acid composition and physicochemical properties to urogastrone has suggested the identity of these polypeptides. Although the mouse and human polypeptides are chemically distinct (16 differences in amino acid sequence), their identical intrinsic biological activities and their ability to share receptor sites with similar affinities has led to the use of the combined term EGF-urogastrone. Reviews: S. Cohen, R. Savage, Recent Prog. Horm. Res. 30, 551-574 (1974); M. D. Hollenberg, Vitam. Horm. 37, 69-110 (1979); D. Gospodarowicz, Annu. Rev. Physiol. 43, 251-263 (1981); P. Walker, J. Endocrinol. Invest. 5, 183-196 (1982); M. Das, Int. Rev. Cytol. 78, 233-256 (1982).