ERBBperhe

ERBBperhe is the Finnish name for the ERBB (also known as EGFR) family of receptor tyrosine kinases. In humans, this family comprises four members: ERBB1 (EGFR/HER1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). The family plays a central role in the regulation of cell growth, differentiation and survival, and is studied across development, physiology and pathology.

All four receptors are single-pass transmembrane proteins with an extracellular ligand-binding domain, a transmembrane segment, and an intracellular tyrosine kinase or kinase-impaired domain. ERBB3 has limited kinase activity and relies on dimerization with other family members to signal, while ERBB2 has no high-affinity ligand and is frequently the preferred dimerization partner for others. Ligands include EGF, transforming growth factor-α, amphiregulin and epiregulin, as well as neuregulins (heregulins) that preferentially activate certain receptors. Binding promotes receptor dimerization and autophosphorylation, initiating downstream signaling.

Activated ERBB receptors stimulate multiple pathways, notably RAS–MAPK, PI3K–AKT and PLCγ, which regulate proliferation, differentiation, migration and survival. Proper ERBB signaling is essential for tissue homeostasis and development; dysregulation can contribute to disease, especially cancer.

Clinical relevance centers on oncogenic alterations such as ERBB2 (HER2) amplification in breast cancer and EGFR mutations or overexpression in various solid tumors. Therapeutic strategies include tyrosine kinase inhibitors (e.g., gefitinib, erlotinib, afatinib, osimertinib for EGFR; others for related receptors) and monoclonal antibodies (cetuximab and panitumumab for EGFR; trastuzumab and pertuzumab for HER2). Resistance mechanisms and predictive biomarkers guide treatment decisions.