PMID:9419975

Citation	Komurasaki, T, Toyoda, H, Uchida, D and Morimoto, S (1997) Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. Oncogene 15:2841-8
Abstract	Epiregulin is a member of the epidermal growth factor (EGF) family, and has certain characteristics that are different from that of EGF, including mitogenic responses and binding to EGF receptor (EGFR). Epiregulin may also have another cell surface receptor and/or induces different receptor heterodimerizations for intracellular signaling. We investigated the binding ability of epiregulin to four ErbB family receptors using four human breast carcinoma cell lines that expressed different subsets of receptors. Chemical cross-linking experiments showed that [125I]epiregulin directly bound to each of EGFR and ErbB-4 but not to ErbB-2 and ErbB-3. Furthermore, although epiregulin stimulated tyrosine phosphorylation of all four ErbB receptors, the main intracellular signal was mediated by ErbB-4 and/or EGFR. The pattern of activation of ErbB family receptors was different from that of other EGF-related ligands. Our findings indicate that ErbB-4 and EGFR are receptors for epiregulin, and suggest that EGF-related ligands transduce signals for different biological responses by the hierarchical mechanism.
Links	PubMed Online version:10.1038/sj.onc.1201458
Keywords	3T3 Cells; Animals; Breast Neoplasms; Epidermal Growth Factor/metabolism; Epidermal Growth Factor/physiology; Humans; Iodine Radioisotopes; Mice; Mice, Inbred BALB C; Phosphorylation; Protein Binding; Proto-Oncogene Proteins/metabolism; Receptor, Epidermal Growth Factor/metabolism; Receptor, erbB-2/metabolism; Receptor, erbB-3; Signal Transduction; Tumor Cells, Cultured; Tyrosine/metabolism
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