Formation of a high affinity heregulin binding site using the soluble extracellular domains of ErbB2 with ErbB3 or ErbB4

ErbB2 functions as a shared signal transducing component for other ErbB receptor family members. Two of these receptors, ErbB3 and ErbB4, bind the heregulin (HRG) or neuregulin family of polypeptide growth factors. Cells expressing ErbB3 alone display a single class of low affinity HRG binding sites...

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Bibliographic Details
Published in:FEBS letters 1998-07, Vol.431 (1), p.102-106
Main Authors: Fitzpatrick, V.Danial, Pisacane, Paul I, Vandlen, Richard L, Sliwkowski, Mark X
Format: Article
Language:English
Subjects:
Affinity modulation
Antibodies, Monoclonal
Binding Sites
Carrier Proteins - metabolism
Cell Line
Cell-Free System
ECD, extracellular domain
EGF, epidermal growth factor
EGFR, epidermal growth factor receptor
ErbB receptor
ErbB Receptors - metabolism
ErbB2-IgG, homodimeric fusion protein between the ECD of ErbB2 with the human IgG heavy chain (other homodimeric constructs are ErbB3-IgG and ErbB4-IgG)
ErbB2/3-IgG, heterodimeric fusion protein between the ECD of ErbB2 and ErbB3 with the human IgG heavy chain (other heterodimeric constructs are ErbB2/4-IgG and ErbB3/4-IgG)
Glycoproteins - metabolism
HER2-neu
HRG, heregulin, also called neu differentiation factor or neuregulin
Humans
Neuregulin
Neuregulin-1
Proto-Oncogene Proteins - metabolism
Receptor, ErbB-2 - metabolism
Receptor, ErbB-3
Receptor, ErbB-4
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Solubility
Transactivation
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Summary:ErbB2 functions as a shared signal transducing component for other ErbB receptor family members. Two of these receptors, ErbB3 and ErbB4, bind the heregulin (HRG) or neuregulin family of polypeptide growth factors. Cells expressing ErbB3 alone display a single class of low affinity HRG binding sites, whereas both high and low affinity binding sites can be measured on cells that co-express both ErbB3 and ErbB2. To assess the interaction of the extracellular domains of ErbB receptors, a series of soluble homodimeric and heterodimeric IgG fusion proteins were constructed. Heregulin binding analysis revealed that a heterodimer composed of either ErbB3 or ErbB4 with ErbB2 is sufficient for the formation of a high affinity binding state. In contrast, heterodimeric ErbB3/4-IgG, as well as homodimeric ErbB3-IgG or ErbB4-IgG, contained only low affinity HRG binding sites. Further evidence for the unique specificity of ErbB2 in generating this high affinity binding site was determined by inhibiting HRG binding with an ErbB2 monoclonal antibody.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(98)00737-6