Figure 2.

2R gave rise to a complex EGFR network. Four EGFR ohnologs have specialized and joint functions: HER2 has apparently lost ligand-binding function, while ErbB3 has almost entirely lost kinase domain function (rectangles, lightning-rod). All six heterodimers can form, with differing signaling capabilities, and duplication and cross-talk between ligands as well as downstream signaling proteins (not shown) further increase the complexity of this system. Abbreviations: AR, amphiregulin; BTC, betacellulin; EGF, epidermal growth factor; EPGN, epigen; EPR, epiregulin; HB-EGF, heparin-binding epidermal growth factor; NGC, neuroglycan-C; NRG, neuregulin; TGFα, transforming growth factor α; TR, tomoregulin.