Figure 4: The epidermal growth factor receptor signalling network. a |Ligand binding to the epidermal growth factor receptor (EGFR) induces dimerization through a receptor-mediated mechanism. Signal diversification is generated by the presence of multiple EGF-like ligands and the formation of different dimeric receptor combinations. b | Receptor dimerization results in cross-autophosphorylation of key tyrosine residues in the cytoplasmic domain, which function as docking sites for downstream signal transducers. EGFR stimulation results in activation of signalling cascades that include the RTK–GRB2–SOS–RAS–RAF– MEK–ERK, PI3K–AKT, PLC??and STAT pathways. EGFR can activate PI3K through RAS-GTP in some cell types. c | EGFR acts as a point of convergence for heterologous signals from G-protein-coupled receptors (GPCRs; metalloprotease-mediated EGFR signal transactivation), cytokine receptors, integrins, membrane depolarization and agents that are induced by cellular stress. The EGFR thereby defines crucial cellular responses, such as proliferation, differentiation, motility and survival. ERK, extracellular-signal-regulated kinase; GEF, guanine-nucleotide-exchange factor; PI3K, phosphatidylinositol 3-kinase; PLC?, phospholipase C?;STAT, signal transducer and activator of transcription.