Epidermal growth factor receptor (extracellular domain) (EGFR (extracellular domain))

The Epidermal growth factor receptor (EGFR) extracellular domain is the portion of the EGFR receptor that is exposed outside the cell, composed of four domains (I-IV): domains I and III are involved in ligand binding (e.g., EGF, TGF-α), while domains II and IV are cysteine-rich and contribute to receptor dimerization control. Ligand engagement induces a structural rearrangement allowing receptor dimerization and subsequent activation of the intracellular tyrosine kinase domain. EGFR extracellular domain is a validated therapeutic target for antibody-based drugs, many of which block ligand binding and prevent aberrant signaling in cancer. Mutations or overexpression of this region confer therapy resistance, aggressive disease phenotype, and are frequently monitored as biomarkers for therapeutic selection.

Other names

EGFR (extracellular region)ErbB1 (extracellular region)Epidermal growth factor receptor (extracellular region)Her1 (extracellular domain)

Competitive inhibition of ligand binding (antibodies, e.g., cetuximab blocks EGF binding to extracellular domain) Prevention of receptor dimerization (antibodies targeting extracellular region induce conformational restriction) Down-regulation and internalization (some antibodies induce receptor endocytosis) Allosteric inhibition of kinase activation via stabilization of inactive extracellular conformations