ErbB1

ErbB1, also known as the epidermal growth factor receptor (EGFR), is a receptor tyrosine kinase of the ErbB family. The human EGFR gene is located on chromosome 7p11.2. The protein has an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. Binding of ligands such as epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-α) induces receptor dimerization, either as homodimers or as heterodimers with other ErbB family members such as ERBB2/HER2, ERBB3, or ERBB4. Autophosphorylation creates docking sites for signaling proteins.

Activation triggers multiple signaling pathways, most notably the RAS–RAF–MEK–ERK and PI3K–AKT–mTOR cascades, with contributions from PLCγ and JAK–STAT signaling. These pathways regulate cell proliferation, survival, differentiation, migration, and metabolism. ErbB1 is widely expressed, with important roles in development and tissue homeostasis.

Dysregulation of ErbB1 is linked to cancer. EGFR amplification or overexpression occurs in glioblastoma and head and neck cancers; activating mutations are common in non-small-cell lung cancer (for example exon 19 deletions and L858R). Therapeutic strategies include epidermal growth factor receptor–targeted tyrosine kinase inhibitors (gefitinib, erlotinib, afatinib) and monoclonal antibodies (cetuximab, panitumumab). Resistance often develops via secondary mutations such as T790M, MET amplification, KRAS or PTEN alterations, or histologic transformation. A cancer-associated variant, EGFRvIII, lacks part of the extracellular domain and is constitutively active in some glioblastomas.

Historically, EGFR signaling emerged from studies of EGF, with cloning and characterization advancing in the 1980s. ErbB1 remains a central node in cell signaling and a major target in precision oncology.