Epidermal growth factor: biology and receptor metabolism

Epidermal growth factor (EGF) is a small (Mr 6045) protein that stimulates cell proliferation in cell culture systems and in intact animals. This growth factor has been isolated from rodents and human material and probably exists in nearly all animal species. In humans EGF has been detected in many body fluids and receptors for the growth factor are also ubiquitous. While the mitogenic activity of EGF has been most frequently reported, it clearly has other functions, such as the inhibition of gastric acid secretion, that are unrelated to mitogenic responses. Correspondingly, receptors for EGF have been localized on cells that are rapidly proliferating and cells that are essentially non-proliferating. Nevertheless, it has not been possible to define experimentally the biological function(s) of the endogenous EGF present in the intact animal. Studies of the mechanism of action of EGF have concentrated, to date, on the plasma membrane receptor that specifically binds this ligand. The receptor is undoubtedly the first cellular component that mediates the eventual biological response(s) of the cell to this extracellular signal. Studies of the EGF receptor have shown that this molecule, which has no subunit structure, functions not only in ligand recognition, but also may produce an intracellular 'second message'. The receptor contains a protein kinase activity that is activated by the binding of EGF and it is this enzymic function that may yield the critical 'second messenger', by phosphorylation of an intracellular protein. Although intracellular targets of this EGF-sensitive protein kinase have been identified, it has not been possible to demonstrate their relevance as regulatory mediators of EGF activity.