Studies on the betacellulin receptor in pancreatic AR42J cells

N. Ishiyama, M. Kanzaki, M. Seno, H. Yamada, I. Kobayashi, I. Kojima

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24 Citations (Scopus)

Abstract

Betacellulin is a member of the epidermal growth factor family and converts pancreatic AR42J cells into insulin-producing cells. This study was conducted to characterise the receptor for betacellulin in AR42J cells. AR42J cells expressed two classes of binding sites for radioactive iodine labelled betacellulin, with Kd values of 4.6 x 10-11 mol/l and 3.0 x 10-10 mol/l. The binding of [125I]betacellulin was inhibited by unlabelled betacellulin in a dose-dependent manner, but epidermal growth factor was 50 fold less effective than betacellulin. Affinity cross-linking showed a [125I]betacellulin-binding protein with a molecular weight of approximately 180 KDa. When this protein was immunoprecipitated with antibody against epidermal growth factor receptors ErbB-1, ErbB-2, ErbB-3 or ErbB-4, it was immunoprecipitated only by the anti-ErbB-1 antibody. When the [125I]betacellulin-labelled proteins were immunoprecipitated with a combination of the four ErbB antibodies, and the unprecipitated proteins were then immunoprecipitated with anti-phosphotyrosine antibody, a 190 KDa protein was observed. Betacellulin induced the tyrosine phosphorylation of ErbB-1, ErbB-2 and ErbB-4. Finally, while 100 pmol/l betacellulin converted all of the AR42J into insulin-producing cells in the presence of activin A, 10 nmol/l epidermal growth factor induced differentiation in only about 30% of the cells. Higher concentrations of epidermal growth factor were less effective. Neu differentiation factor in the presence or absence of epidermal growth factor was ineffective. These results indicate that betacellulin binds to ErbB-1 and possibly another protein with a molecular weight of 190 KDa. The latter betacellulin-binding protein may be involved in the differentiation-inducing activity of betacellulin.

Original languageEnglish
Pages (from-to)623-628
Number of pages6
JournalDiabetologia
Volume41
Issue number6
DOIs
Publication statusPublished - Jun 18 1998

Keywords

  • Betacellulin
  • Differentiation
  • Epidermal growth factor
  • Epidermal growth factor receptor
  • ErbB

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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  • Cite this

    Ishiyama, N., Kanzaki, M., Seno, M., Yamada, H., Kobayashi, I., & Kojima, I. (1998). Studies on the betacellulin receptor in pancreatic AR42J cells. Diabetologia, 41(6), 623-628. https://doi.org/10.1007/s001250050959