Jones J T, Akita R W, Sliwkowski M X
Genentech, Inc., Department of Molecular Oncology, South San Francisco, CA 94080, USA.
FEBS Lett. 1999 Mar 26;447(2-3):227-31. doi: 10.1016/s0014-5793(99)00283-5.
ErbB receptor activation is a complex process and is dependent upon the type and number of receptors expressed on a given cell. Previous studies with defined combinations of ErbB receptors expressed in mammalian cells have helped elucidate specific biological responses for many of the recognized gene products that serve as ligands for these receptors. However, no study has examined the binding of these ligands in a defined experimental system. To address this issue, the relative binding affinities of the egf domains of eleven ErbB ligands were measured on six ErbB receptor combinations using a soluble receptor-ligand binding format. The ErbB2/4 heterodimer was shown to bind all ligands tested with moderate to very high affinity. In contrast, ErbB3 showed much more restrictive ligand binding specificity and measurable binding was observed only with heregulin, neuregulin2beta, epiregulin and the synthetic heregulin/egf chimera, biregulin. These studies also revealed that ErbB2 preferentially enhances ligand binding to ErbB3 or ErbB4 and to a lesser degree to ErbB1.
表皮生长因子受体（ErbB）的激活是一个复杂的过程，并且取决于特定细胞上所表达的受体的类型和数量。先前对在哺乳动物细胞中表达的特定组合的ErbB受体的研究，有助于阐明许多作为这些受体配体的已知基因产物的特定生物学反应。然而，尚无研究在一个明确的实验系统中检测这些配体的结合情况。为了解决这个问题，我们使用可溶性受体-配体结合形式，在六种ErbB受体组合上测量了11种ErbB配体的表皮生长因子（EGF）结构域的相对结合亲和力。结果显示，ErbB2/4异二聚体能够以中等至非常高的亲和力结合所有测试的配体。相比之下，ErbB3表现出更具限制性的配体结合特异性，仅在与神经调节蛋白、神经调节蛋白2β、表皮调节素以及合成的神经调节蛋白/表皮生长因子嵌合体双调蛋白结合时，才能观察到可测量的结合。这些研究还表明，ErbB2优先增强配体与ErbB3或ErbB4的结合，在较小程度上也增强与ErbB1的结合。
