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.
Kinugasa
Yumi
Y
Division of Biochemistry and Molecular Biology, Department of Cellular and Molecular Genetics, Ehime University School of Medicine, Shitukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan.
Ishiguro
Hiroshi
H
Tokita
Yoshihito
Y
Oohira
Atsuhiko
A
Ohmoto
Hiroshi
H
Higashiyama
Shigeki
S
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006224:Cricetinae; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D020880:Neuregulins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009500:Neutralization Tests; D018739:Oncogene Proteins v-erbB / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D011508:Chondroitin Sulfate Proteoglycans; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020880:Neuregulins; D018739:Oncogene Proteins v-erbB; D011994:Recombinant Proteins; C492323:neuroglycan C, human