Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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CHO Cells
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Cell Line, Tumor
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Chondroitin Sulfate Proteoglycans / chemistry
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Chondroitin Sulfate Proteoglycans / genetics
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Chondroitin Sulfate Proteoglycans / physiology*
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Cricetinae
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Humans
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In Vitro Techniques
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / physiology*
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology
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Neuregulins / chemistry
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Neuregulins / genetics
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Neuregulins / physiology*
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Neutralization Tests
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Oncogene Proteins v-erbB / metabolism
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Protein Binding
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
Substances
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Chondroitin Sulfate Proteoglycans
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Membrane Proteins
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Nerve Tissue Proteins
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Neuregulins
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Oncogene Proteins v-erbB
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Recombinant Proteins
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neuroglycan C, human