Epiregulin Is a Potent Pan-ErbB Ligand That Preferentially Activates Heterodimeric Receptor Complexes

摘要: The ErbB signaling network consists of four transmembrane receptor tyrosine kinases and more than a dozen ligands sharing an epidermal growth factor (EGF) motif. multiplicity ErbB-specific is incompletely understood in terms signal specificity because all molecules through partially overlapping pathways. Here we addressed the action epiregulin, recently isolated ligand ErbB-1. By employing set factor-dependent cell lines engineered to express individual ErbBs or their combinations, found that epiregulin broadest EGF-like so far characterized: not only does it stimulate homodimers both ErbB-1 ErbB-4, also activates possible heterodimeric complexes. Consistent with its relaxed selectivity, binds various combinations affinity approximately 100-fold lower stringent including EGF. Nevertheless, epiregulin's upon most transmits potent mitogenic This remarkable discrepancy between binding bioactivity permitted by mechanism prevents down-regulation, results weak, but prolonged, state activation.