Falls Douglas L
Center for Neurodegenerative Disease, Department of Neurology, Emory University, Atlanta, GA 30322, USA.
Exp Cell Res. 2003 Mar 10;284(1):14-30. doi: 10.1016/s0014-4827(02)00102-7.
The neuregulins (NRGs) are cell-cell signaling proteins that are ligands for receptor tyrosine kinases of the ErbB family. The neuregulin family of genes has four members: NRG1, NRG2, NRG3, and NRG4. Relatively little is known about the biological functions of the NRG2, 3, and 4 proteins, and they are considered in this review only briefly. The NRG1 proteins play essential roles in the nervous system, heart, and breast. There is also evidence for involvement of NRG signaling in the development and function of several other organ systems, and in human disease, including the pathogenesis of schizophrenia and breast cancer. There are many NRG1 isoforms, raising the question "Why so many neuregulins?" Study of mice with targeted mutations ("knockout mice") has demonstrated that isoforms differing in their N-terminal region or in their epidermal growth factor (EGF)-like domain differ in their in vivo functions. These differences in function might arise because of differences in expression pattern or might reflect differences in intrinsic biological characteristics. While differences in expression pattern certainly contribute to the observed differences in in vivo functions, there are also marked differences in intrinsic characteristics that may tailor isoforms for specific signaling requirements, a theme that will be emphasized in this review.
神经调节蛋白（NRGs）是细胞间信号传导蛋白，是ErbB家族受体酪氨酸激酶的配体。神经调节蛋白基因家族有四个成员：NRG1、NRG2、NRG3和NRG4。人们对NRG2、3和4蛋白的生物学功能了解相对较少，本综述仅对它们进行简要讨论。NRG1蛋白在神经系统、心脏和乳腺中发挥着重要作用。也有证据表明NRG信号参与了其他几个器官系统的发育和功能，以及人类疾病，包括精神分裂症和乳腺癌的发病机制。有许多NRG1亚型，这就引出了一个问题：“为什么会有这么多神经调节蛋白？”对具有靶向突变的小鼠（“基因敲除小鼠”）的研究表明，在其N端区域或表皮生长因子（EGF）样结构域不同的亚型在体内功能上存在差异。这些功能差异可能是由于表达模式的不同引起的，也可能反映了内在生物学特性的差异。虽然表达模式的差异肯定导致了观察到的体内功能差异，但内在特性也存在显著差异，这些差异可能使亚型适应特定的信号需求，这将是本综述强调的一个主题。
