神经调节蛋白-3（NRG3）：一种新的在神经组织中高表达的蛋白，可结合并激活ErbB4。
Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4.
作者信息
Zhang D, Sliwkowski M X, Mark M, Frantz G, Akita R, Sun Y, Hillan K, Crowley C, Brush J, Godowski P J
机构信息
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080, USA.
出版信息
Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9562-7. doi: 10.1073/pnas.94.18.9562.
We describe the identification of Neuregulin-3 (NRG3), a novel protein that is structurally related to the neuregulins (NRG1). The NRG1/neuregulins are a diverse family of proteins that arise by alternative splicing from a single gene. These proteins play an important role in controlling the growth and differentiation of glial, epithelial, and muscle cells. The biological effects of NRG1 are mediated by receptor tyrosine kinases ErbB2, ErbB3, and ErbB4. However, genetic studies have suggested that the activity of ErbB4 may also be regulated in the central nervous system by a ligand distinct from NRG1. NRG3 is predicted to contain an extracellular domain with an epidermal growth factor (EGF) motif, a transmembrane domain, and a large cytoplasmic domain. We show that the EGF-like domain of NRG3 binds to the extracellular domain of ErbB4 in vitro. Moreover, NRG3 binds to ErbB4 expressed on cells and stimulates tyrosine phosphorylation of this receptor. The expression of NRG3 is highly restricted to the developing and adult nervous system. These data suggest that NRG3 is a novel, neural-enriched ligand for ErbB4.
我们描述了神经调节蛋白-3（NRG3）的鉴定，它是一种与神经调节蛋白（NRG1）在结构上相关的新型蛋白质。NRG1/神经调节蛋白是一个多样化的蛋白质家族，由单个基因通过可变剪接产生。这些蛋白质在控制神经胶质细胞、上皮细胞和肌肉细胞的生长与分化中发挥重要作用。NRG1的生物学效应由受体酪氨酸激酶ErbB2、ErbB3和ErbB4介导。然而，遗传学研究表明，在中枢神经系统中，ErbB4的活性也可能由一种不同于NRG1的配体调节。预测NRG3含有一个带有表皮生长因子（EGF）基序的细胞外结构域、一个跨膜结构域和一个大的细胞质结构域。我们发现，NRG3的EGF样结构域在体外与ErbB4的细胞外结构域结合。此外，NRG3与细胞上表达的ErbB4结合，并刺激该受体的酪氨酸磷酸化。NRG3的表达高度局限于发育中的和成年的神经系统。这些数据表明，NRG3是一种新型的、在神经组织中富集的ErbB4配体。
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