Allosteric regulation of the epidermal growth factor receptor kinase

S INCE the pioneering discoveries of nerve growth factor (24) and epidermal growth factor (EGF) ~ (8), it has become clear that polypeptide growth factors play a crucial role in the proliferation, survival, and differentiation of eukaryotic cells. Since then, many new growth factors have been discovered; some of them exert their biological effects on specific cell lineages, while others have broad specificity for many cell types from many tissues (17). EGF, because it is the best characterized growth factor, may serve as a model system for exploring the molecular mechanisms underlying mitogenic stimulation. Moreover, it has become clear that specific lesions in the EGF receptor, or abnormal expression of growth factors that mediate their effects by activating the EGF receptors, may be associated with certain cancers. Therefore, the elucidation of the mechanism of action of EGF will certainly provide important clues to fundamental questions concerning the action of growth factors in general and their role in oncogenesis.