Fitzpatrick V D, Pisacane P I, Vandlen R L, Sliwkowski M X
Genentech, Inc., Department of Molecular Oncology, South San Francisco, CA 94080, USA.
FEBS Lett. 1998 Jul 10;431(1):102-6. doi: 10.1016/s0014-5793(98)00737-6.
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.
ErbB2作为其他ErbB受体家族成员的共享信号转导组件发挥作用。其中两种受体，即ErbB3和ErbB4，可结合神经调节蛋白（HRG）或神经调节蛋白家族的多肽生长因子。单独表达ErbB3的细胞显示出一类低亲和力的HRG结合位点，而在共表达ErbB3和ErbB2的细胞上则可检测到高亲和力和低亲和力的结合位点。为了评估ErbB受体胞外域之间的相互作用，构建了一系列可溶性同二聚体和异二聚体IgG融合蛋白。神经调节蛋白结合分析表明，由ErbB3或ErbB4与ErbB2组成的异二聚体足以形成高亲和力结合状态。相比之下，异二聚体ErbB3/4-IgG以及同二聚体ErbB3-IgG或ErbB4-IgG仅含有低亲和力的HRG结合位点。通过用ErbB2单克隆抗体抑制HRG结合，确定了ErbB2在产生这种高亲和力结合位点方面独特特异性的进一步证据。
