Figure 1. Model of oncogenesis driven by mutant ErbB3. Epidermal growth factor receptor 3 (EGFR3; HER3; ErbB3) is a receptor tyrosine kinase that is ineffective at activating downstream cellular signaling pathways by itself owing to its impaired kinase domain. Instead, downstream signaling via ErbB3 depends on the binding of an appropriate ligand to the receptor. As reported in Jaiswal et al., oncogenic mutations in ERBB3 are primarily found in the receptor's extracellular domain and render the protein ligand-independent. Binding of a ligand to the wild-type ErbB3 receptor (I) promotes its ability to undergo dimerization with HER2 (EGFR2; ErbB2; neu), which has an active kinase domain. The resulting HER2-ErbB3 heterodimer can then activate downstream signaling pathways. Without an appropriate ligand (II), wild-type ErbB3 is unable to form a heterodimer with HER2 and activate downstream signaling pathways in an effective manner. Oncogenic mutant ErbB3 can form a heterodimer with HER2 in the absence of an appropriate ligand (III) and activate downstream signaling pathways. Addition of an ErbB3 ligand can further stimulate this activity.