Members of the human epidermal growth factor receptor (HER) family of transmembrane receptor tyrosine kinases (HER1/EGFR; HER2; HER3; HER4) and their respective ligands constitute a robust biologic system that plays a key role in the regulation of cell-proliferative growth, survival, and differentiation. Ligand-bound monomeric HER receptors form homo- or heterodimers, which in turn activate their respective autokinase activities, leading to self-phosphorylation of c-terminus tyrosine residues serving as docking sites for adaptor proteins that activate downstream growth and survival signaling cascades. EGFR/HER3 heterodimer are potent activators of PI3K signaling, which in breast and other solid tumors, represents an important oncogenic signaling unit.
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