The EGFR (Epidermal Growth Factor Receptor) is a transmembrane glycoprotein located on the cell membrane and belongs to the ErbB receptor tyrosine kinase family (HER1/ErbB1). Its structure consists of three main domains: an extracellular region, a transmembrane region, and an intracellular region. The extracellular region contains four domains (I-IV), with domains II and IV being cysteine-rich and responsible for binding ligands (such as EGF and TGF-伪), leading to receptor dimerization. The transmembrane region is a single 伪-helix that anchors the receptor in the cell membrane. The intracellular region possesses tyrosine kinase activity and includes a juxtamembrane domain, a kinase domain (with an ATP-binding site), and a C-terminal regulatory tail containing multiple autophosphorylation sites (e.g., Y992, Y1045, Y1068). EGFR activates downstream signaling pathways such as RAS/RAF/MEK/ERK and PI3K/AKT, regulating cell proliferation, differentiation, migration, and survival. Mutations or overexpression of EGFR are strongly associated with various cancers, including lung and colorectal cancers, making it a key target for drugs like gefitinib and osimertinib.
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