The biosynthetic precursor of epidermal growth factor and the mechanism of its processing.

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Abstract
The biosynthesis of epidermal growth factor (EGF) was studied in mouse submaxillary glands incubated with L-[35S]cystine. EGF and EGF-like proteins were isolated from the gland homogenates by immunoprecipitation with anti-EGF antiserum. The major species appearing after short labeling periods is significantly larger (MW 9000) than EGF. The label in the MW 9000 species plateaus after 1 h whereas that in EGF continuously increases. When glands are chased with unlabeled L-cystine after a brief period of labeling, the MW 9000 peak decreases and a corresponding amount of label appears in EGF. The MW 9000 species was isolated from boiled homogenates in which it accounts for .apprxeq. 1% of the total EGF content. It contains 5 of the 6 chymotryptic peptides of EGF and a 6th peptide which is a modified form of the COOH-terminal chymotryptic peptide of EGF. Of the arginyl esteropeptidases, .gamma. subunit of 7S nerve growth factor, .beta.-endopeptidase, trypsin and EGF-binding protein, only the latter converts the isolated MW 9000 species of EGF. The extrapeptide material released in the conversion comes from the COOH terminus of the MW 9000 species. The MW 9000 species is a biosynthetic precursor of EGF and that the EGF-binding protein is the specific intracellular cleaving enzyme that converts the precursor to EGF. In the process, the stable high MW complex of EGF is formed.