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- _7 value "Figure 1 | ERBB receptors, ligands, dimers and downstream signalling pathways. a | Members of the epidermal growth factor (EGF) family of growth factors are ligands for the ERBB receptors. Ligand binding to ERBB receptors induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues within the cytoplasmic tail. These phosphorylated residues serve as docking sites for a range of proteins, the recruitment of which leads to the activation of intracellular signalling pathways. None of the ligands bind ERBB2, but ERBB2 is the preferred dimerization partner for all the other ERBB receptors. ERBB3 has impaired kinase activity and only acquires signalling potential when it is dimerized with another ERBB receptor, such as ERBB2. Overexpression of ERBB2 in tumours leads to constitutive activation of ERBB2, presumably because of increased receptor concentrations at the plasma membrane. Many of these tumours contain phosphorylated ERBB3, which couples ERBB2 to the phosphatidylinositol 3-kinase (PI3K)?AKT pathway128." provenance.