Neuroglycan C, a novel member of the neuregulin family.
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 phosphorylation 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-Fc, ErbB2-Fc or ErbB4-Fc. A newly established anti-ErbB3 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.
Mesh Terms:
Amino Acid Sequence, Animals, CHO Cells, Cell Line, Tumor, Chondroitin Sulfate Proteoglycans, Cricetinae, Humans, In Vitro Techniques, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Neuregulins, Neutralization Tests, Oncogene Proteins v-erbB, Protein Binding, Protein Structure, Tertiary, Recombinant Proteins, Sequence Homology, Amino Acid
Amino Acid Sequence, Animals, CHO Cells, Cell Line, Tumor, Chondroitin Sulfate Proteoglycans, Cricetinae, Humans, In Vitro Techniques, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Neuregulins, Neutralization Tests, Oncogene Proteins v-erbB, Protein Binding, Protein Structure, Tertiary, Recombinant Proteins, Sequence Homology, Amino Acid
Biochem. Biophys. Res. Commun.
Date: Sep. 03, 2004
PubMed ID: 15358134
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