Neuroglycan C, a novel member of the neuregulin family
Neuroglycan C, a novel member of the neuregulin family
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DOI：
10.1016/j.bbrc.2004.07.066
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发表时间：
2004-09-03
影响因子：
3.1
通讯作者：
Higashiyama, S
中科院分区：
文献类型：
--
作者：
Kinugasa, Y;Ishiguro, H;Higashiyama, S
神经多糖C(NGC)是一种跨膜的硫酸软骨素蛋白多糖，主要在脑内表达，具有EGF样胞外域。本研究的目的是确定NGC是否可以激活ErbB酪氨酸激酶。重组人NGC胞外区诱导ErbB2和ErbB3的酪氨酸磷酸化以及人乳腺癌细胞株T47D和MDA-MB-453的生长。体外下拉实验表明，NGC可直接与重组ErbB3-免疫球蛋白Fc融合蛋白(ErbB3-Fc)结合，但不能与ErbB1-Fe、ErbB2-Fe或ErbB4-Fc结合。一种新建立的抗ErB3中和单抗(#5C3)几乎完全阻断NGC诱导的MDA-MB-453细胞中ErbB的激活。综上所述，这些数据表明，NGC是一种活性生长因子和ErbB3的直接配体，NGC反式激活ErbB2。因此，NGC应该被归类为NeuRegin家族的第六个成员(neuRegin-6)。(C)2004 Elsevier Inc.保留所有权利。
Neuroglycan C (NGC) is a transmembrane chondroitin sulfate proteoglycan expressed predominantly in the brain that possesses an EGF-like extracellular domain. The goal of the present study was to determine whether NGC may activate ErbB tyrosine kinases. A recombinant human NGC extracellular domain induced tyrosine phosphorytation of ErbB2 and ErbB3 as well as cell growth of the human breast tumor cell lines, T47D and MDA-MB-453. In vitro pull-down assay revealed that NGC could directly bind to a recombinant ErbB3-immunoglobulin Fc fusion protein (ErbB3-Fc) but not to ErbB1-Fe, ErbB2-Fe or ErbB4-Fc. A newly established anti-ErB3 neutralizing monoclonal antibody (#5C3) almost completely blocked NGC-induced ErbB activation in MDA-MB-453 cells. Taken together, these data indicate that NGC is an active growth factor and a direct ligand for ErbB3 and that NGC transactivates ErbB2. Thus, NGC should be classified as the sixth member (neuregulin-6) of the neuregulin family. (C) 2004 Elsevier Inc. All rights reserved.