Citri Ami, Skaria Kochupurakkal Bose, Yarden Yosef
Department of Biological Regulation, The Weizmann Institute of Science, 76100, Rehovot, Israel.
Exp Cell Res. 2003 Mar 10;284(1):54-65. doi: 10.1016/s0014-4827(02)00101-5.
ErbB-2 (also called HER2/neu) and ErbB-3 are closely related to the epidermal growth factor receptor (EGFR/ErbB-1), but unlike EGFR, ErbB-2 is a ligandless receptor, whereas ErbB-3 lacks tyrosine kinase activity. Hence, both ErbB-2 and ErbB-3 are active only in the context of ErbB heterodimers, and ErbB-2. ErbB-3 heterodimers, which are driven by neuregulin ligands, are the most prevalent and potent complexes. These stringently controlled heterodimers are repeatedly employed throughout embryonic development and dictate the establishment of several cell lineages through mesenchyme-epithelial inductive processes and the interactions of neurons with muscle, glia, and Schwann cells. Likewise, the potent combination of signaling pathways engaged by the heterodimers drives an aggressive phenotype of tumors of secretory epithelia, including breast and lung cancers. This review highlights recent structural insights into the mechanism of ligand-induced heterodimer formation, and concentrates on signaling pathways employed by ErbB-2 and ErbB-3 in normal and in malignant cells.
ErbB-2（也称为HER2/neu）和ErbB-3与表皮生长因子受体（EGFR/ErbB-1）密切相关，但与EGFR不同的是，ErbB-2是一种无配体受体，而ErbB-3缺乏酪氨酸激酶活性。因此，ErbB-2和ErbB-3仅在ErbB异二聚体的情况下才具有活性，并且ErbB-2-ErbB-3异二聚体由神经调节蛋白配体驱动，是最普遍且最有效的复合物。这些受到严格控制的异二聚体在整个胚胎发育过程中被反复利用，并通过间充质-上皮诱导过程以及神经元与肌肉、神经胶质细胞和雪旺细胞的相互作用来决定几种细胞谱系的建立。同样，异二聚体所涉及的信号通路的强大组合驱动了分泌上皮肿瘤（包括乳腺癌和肺癌）的侵袭性表型。本综述重点介绍了近期对配体诱导异二聚体形成机制的结构见解，并着重探讨了ErbB-2和ErbB-3在正常细胞和恶性细胞中所采用的信号通路。
