EGF was originally discovered in crude preparations of nerve growth factor prepared from mouse submaxillary glands as an activity that induced early eyelid opening, incisor eruption, hair growth inhibition, and stunting of growth when injected into newborn mice. Human EGF was isolated from urine based on its inhibitory effect on gastric secretion and named urogastrone, accordingly. EGF is prototypic of a family of growth factors that are derived from membrane-anchored precursors. All members of this family are characterized by the presence of at least one EGF structural unit (defined by the presence of a conserved 6 cysteine motif that forms three disulfide bonds) in their extracellular domain. EGF is initially synthesized as a 130 kDa precursor transmembrane protein containing 9 EGF units. The mature soluble EGF sequence corresponds to the EGF unit located proximal to the transmembrane domain. The membrane EGF precursor is capable of binding to the EGF receptor and was reported to be biologically active.
A wide variety of biological effects have been ascribed to EGF and other members of the EGF family. The best documented activity of EGF is its ability to promote proliferation and differentiation of mesenchymal and epithelial cells. EGF is a mitogen for fibroblasts, epithelial and endothelial cells, and promotes colony formation of epidermal cells in culture. EGF induces epithelial development, promotes angiogenesis, and inhibits gastric acid secretion.
A DNA sequence encoding the mature human EGF protein (Accession # P01133; Bell, G.I. et al., 1986, Nucleic Acids Res. 14(21):8427 - 8446) was expressed in E. coli.