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FIGURE 16-17 The HER family of receptors and their ligands. Humans and mice express four receptor tyrosine kinases, denoted HER1, 2, 3, and 4 in humans and Erb-B1, 2, 3, and 4 in mice and other animals. Only the extracellular domains of these receptors are depicted here. These receptors bind epidermal growth factor (EGF) and the other EGF family members: heparin-binding EGF (HB-EGF), transforming growth factor α (TGF-α), amphiregulin (AREG), epiregulin (EREG), epigen (EPGN), betacellulin (BTC), and the four neuregulins. Note that Erb-B2 (HER2), which does not directly bind a ligand, exists in a conformation that is very similar to that of the activated Erb-B1 with a bound EGF. Erb-B2 can form a heterodimer with ligand-activated Erb-B1, 3, or 4; thus Erb-B2 facilitates signaling by all EGF family members. Erb-B3 (HER3) has a very poorly active kinase domain and can signal only when complexed with Erb-B2.
[Erb-B1 data from K. M. Ferguson et al., 2003, Mol. Cell 11:507, PDB ID 1nql. Erb-B2 data from H.-S. Cho et al., 2003, Nature 421:756, PDB ID 1n8z. Erb-B3 data from H. S. Cho and D. J. Leahy, 2002, Science 297:1330, PDB ID 1m6b. Erb-B4 data from S. Bouyain et al., 2005, Proc. Natl. Acad. Sci. USA 102:15024, PDB ID 1ahx. EFG and Erb-B1 data from H. Ogiso et al., 2002, Cell 110:775, PDB ID 1ivo.]