Functional and structural characteristics of EGF and its receptor and their relationship to transforming proteins

Abstract

Epidermal growth factor (EGF) is a peptide which effects the growth and/or differentiated functions of many cell types. Several pieces of evidence indicate that EGF and its receptor may play a role in carcinogenesis. Functional and structural characteristics of EGF and its receptor and their relationship to transforming proteins are discussed. EGF has extensive homology with alpha‐transforming growth factor (alpha‐TGF), which may actually be an embryonic form of EGF. Nevertheless, both EGF and alpha‐TGF elicit transformation‐associated phenotypes in target cells under certain conditions. EGF effects are mediated by a receptor present on the plasma membrane. The EGF receptor is a highly complex protein having several functions in addition to binding EGF in a highly specific manner. One of these functions is to phosphorylate tyrosyl residues on certain proteins. This activity is similar to that expressed by the src family of oncogene‐encoded proteins. Besides sharing functional homology the EGF receptor also exhibits structural homology to several oncogene‐encoded proteins. The v‐erb‐B‐transforming protein has a striking extent of homology (95%) to the cytoplasmic portion of the EGF receptor. These data support the concept that some aspect of EGF‐stimulated metabolism is involved in cellular transformation.