General structure

Epidermal growth-factor receptor (EGFR) proteins or erythroblastic leukemia viral oncogene homolog (ERBB) proteins are a group of transmembrane receptors with intrinsic tyrosine kinase activity. The EGFR family is one of the most important groups of transmembrane cell surface receptors that integrate extra-cellular signals (e.g. growth factors, cytokines, and hormones) to drive multiple critical cellular processes, including cell proliferation, differentiation, and survival, via localized paracrine signals (1). EGFR family proteins are classified as subclass I receptor tyrosine kinases (RTKs; Figure 79.1), containing four structurally related RTKs (2): EGFR (also known as ERBB-1/HER1), ERBB-2 (HER2 in humans and Neu in rodents), ERBB-3 (HER3), and ERBB-4 (HER4). Each EGFR family receptor has an extra-cellular ligand-binding domain, a single α-helix transmembrane domain, an intra-cellular tyrosine kinase domain (with the exception of ERBB-3/HER3) and a cytoplasmic tail with tyrosine autophosphorylation sites (3; Figure 79.2). Although all four of these members share a similar domain structure, each has unique properties. EGFR (ERBB1) and ERBB4 have several known extra-cellular ligands and tyrosine-kinase activity on their cytoplasmic tail. ERBB2 has a similar active tyrosine-kinase domain. However, no direct ligand for ERBB2 has been identified. The other member, ERBB3 is characterized by a lack of tyrosine-kinase activity, although it binds to its extra-cellular ligands (4,5).