Neuroglycan C, a novel member of the neuregulin family

被引：49

作者：

Kinugasa, Y

Ishiguro, H

Tokita, Y

Oohira, A

Ohmoto, H

Higashiyama, S ^{[1
]}

机构：

[1] Ehime Univ, Sch Med, Dept Cellular & Mol Genet, Div Biochem & Mol Biol, Shigenobu, Ehime 7910295, Japan

[2] Carna Biosci Inc, Kobe, Hyogo 6508543, Japan

[3] Aichi Human Serv Ctr, Inst Dev Res, Dept Perinatol, Kasugai, Aichi 4800392, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 321卷 / 04期

关键词：

neuroglycan C; neuregulin; EGF; ErbB; tyrosine kinase; growth factor; chondroitin sulfate; proteoglycan;

D O I：

10.1016/j.bbrc.2004.07.066

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1045 / 1049

页数：5

共 27 条

[1] The ErbB signaling network in embryogenesis and oncogenesis: Signal diversification through combinatorial ligand-receptor interactions [J].