| First Author | Tzahar E | Year | 1997 |
| Journal | EMBO J | Volume | 16 |
| Issue | 16 | Pages | 4938-50 |
| PubMed ID | 9305636 | Mgi Jnum | J:42457 |
| Mgi Id | MGI:1095780 | Doi | 10.1093/emboj/16.16.4938 |
| Citation | Tzahar E, et al. (1997) Bivalence of EGF-like ligands drives the ErbB signaling network. EMBO J 16(16):4938-50 |
| abstractText | Signaling by epidermal growth factor (EGF)-like ligands is mediated by an interactive network of four ErbB receptor tyrosine kinases, whose mechanism of ligand-induced dimerization is unknown. We contrasted two existing models: a conformation-driven activation of a receptor-intrinsic dimerization site and a ligand bivalence model. Analysis of a Neu differentiation factor (NDF)-induced heterodimer between ErbB-3 and ErbB-2 favors a bivalence model; the ligand simultaneously binds both ErbB-3 and ErbB-2, but, due to low-affinity of the second binding event, ligand bivalence drives dimerization only when the receptors are membrane anchored. Results obtained with a chimera and isoforms of NDF/neuregulin predict that each terminus of the ligand molecule contains a distinct binding site. The C-terminal low-affinity site has broad specificity, but it prefers interaction with ErbB-2, an oncogenic protein acting as a promiscuous low-affinity subunit of the three primary receptors. Thus, ligand bivalence enables signal diversification through selective recruitment of homo- and heterodimers of ErbB receptors, and it may explain oncogenicity of erbB-2/HER2. |
