Neuroglycan C, a novel member of the neuregulin family

Biochem Biophys Res Commun. 2004 Sep 3;321(4):1045-9. doi: 10.1016/j.bbrc.2004.07.066.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Cell Line, Tumor
  • Chondroitin Sulfate Proteoglycans / chemistry
  • Chondroitin Sulfate Proteoglycans / genetics
  • Chondroitin Sulfate Proteoglycans / physiology*
  • Cricetinae
  • Humans
  • In Vitro Techniques
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Neuregulins / chemistry
  • Neuregulins / genetics
  • Neuregulins / physiology*
  • Neutralization Tests
  • Oncogene Proteins v-erbB / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid


  • Chondroitin Sulfate Proteoglycans
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Neuregulins
  • Oncogene Proteins v-erbB
  • Recombinant Proteins
  • neuroglycan C, human