A historical perspective of the EGF receptor and related systems.

Since the isolation of epidermal growth factor (EGF) from mouse submaxillary glands in the early 1950s by Cohen and coworkers, this growth factor has been shown to have various effects on numerous cellular systems. The biological and physiological role that EGF plays during development and in adult animals led to the identification of its receptor (EGFR) as well as the other members of the EGF family of growth factors and their receptors. In this chapter we provide a historical overview of the discovery of EGF, identification of the other members of EGF family, early studies on the actions of EGF, as well as the discovery and structural characterization of its receptor. Further, we have reviewed the transactivation of the EGFR by agonists for G protein-coupled receptors (GPCRs) and other extracellular stimuli unrelated to EGF-like ligands. Finally, an overview of the role of the EGFR family members in various diseases, including different forms of cancer, is provided.