The biosynthetic precursor of epidermal growth factor and the mechanism of its processing.
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 (Mr, 9000) than EGF. The label in the Mr 9000 species plateaus after 1 hr whereas tha in EGF continuously increases. When glands are chased with unlabeled L-cystine after a brief period of labeling, the Mr 9000 peak decreases and a corresponding amount of label appears in EGF. The Mr 9000 species was isolated from boiled homogenates in which it accounts for approximately 1% of the total EGF content. It contains five of the six chymotryptic peptides of EGF and a sixth 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 Mr 9000 species to EGF. The extrapeptide material released in the conversion comes from the COOH terminus of the Mr 9000 species. These results suggest that the Mr 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 molecular weight complex of EGF is formed.
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003553:Cystine / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008970:Molecular Weight; D010452:Peptide Biosynthesis; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*
D002352:Carrier Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D003553:Cystine; D004815:Epidermal Growth Factor; D010450:Endopeptidases