ERBB2 and neoplasm: Like other family members, HER2 is structurally constituted by three domains: an extracellular domain responsible for ligand binding and homo/heterodimers formation, a transmembrane domain that makes a single pass through the plasma membrane and a tyrosine kinase (TK) domain responsible for activation of two key signaling pathways, namely, the RAS/RAF/MAPK pathway, which stimulates proliferation, and the PI3K/Akt pathway, which promotes tumor cell survival.