title: ErbB2 dephosphorylation and anti-proliferative effects of neuregulin-1 in ErbB2-overexpressing cells; re-evaluation of their low-affinity interaction.
abstract: Neuregulin-1 binds to ErbB3 and ErbB4 and regulates cancer proliferation and differentiation. Neuregulin-1 had been suggested to also react with ErbB2, but this argument becomes controversial. Here, we re-evaluated the cellular responses and ErbB2 interaction of neuregulin-1 in ErbB2 overexpressing cell lines. In a competitive ligand-binding assay, we detected significant replacement of [(35)S]-labeled neuregulin-1 with nano molar ranges of cold neuregulin-1 in L929 cells expressing ErbB2 alone and SKOV3 cells carrying sulf-1 cDNA but not in these parental cells. The concentration of neuregulin-1 significantly decreased thymidine incorporation and phosphorylation of ErbB2 (Tyr877, Tyr1396, and Tyr1121) in ErbB2-overexpressing cancer cells as well as in L929 cells expressing ErbB2. A crosslinking assay ascertained the presence of neuregulin-1 immunoreactivity in the ErbB2 immune complexes of L929 expressing ErbB2 alone. These results suggest that the higher concentrations of neuregulin-1 exert an anti-oncogenic activity to attenuate ErbB2 auto-phosphorylation potentially through its low-affinity interaction with ErbB2.
authors: Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan.
authors: Ran
authors: R
authors: Wang
authors: Yuriko
authors: Y
authors: Iwakura
authors: Kazuaki
authors: K
authors: Araki
authors: Kazuko
authors: K
authors: Keino-Masu
authors: Masayuki
authors: M
authors: Masu
authors: Xue-yi
authors: XY
authors: Wang
authors: Nobuyuki
authors: N
authors: Takei
authors: Shigeki
authors: S
authors: Higashiyama
authors: Hiroyuki
authors: H
authors: Nawa
mesh_terms: D001667:Binding, Competitive; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D020890:Neuregulin-1 / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism
chemical_list: D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3