Processing and juxtacrine activity of membrane-anchored betacellulin

Hiroko Tada, Reiko Sasada, Yasuko Kawaguchi, Itaru Kojima, William J. Gullick, David S. Salomon, Koichi Igarashi, Masaharu Seno, Hidenori Yamada

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Abstract

Betacellulin (BTC) was originally isolated as a secreted growth factor from a mouse pancreatic β-tumor cell line, whereas the cDNA sequence predicts that BTC is synthesized as a larger transmembrane protein. In the present study, we have characterized the membrane-anchored forms of BTC, using Chinese hamster ovary (CHO) cells, mouse fibroblast A9 cells, and a human breast cancer cell line MCF-7, all of which were stably transfected with human BTC cDNA. A9 and MCF-7 transfectants produced membrane-anchored BTC isoforms of 21, 25, 29, and 40 kDa on the cell surface, as well as a secreted BTC isoform. CHO transfectants secreted little BTC but accumulated the membrane-anchored isoforms. The cleavage of the membrane-anchored forms to release a secreted from of BTC was not enhanced by biological mediators such as a phorbol ester, which stimulates the cleavage of other membrane- anchored growth factors. The membrane-anchored forms of BTC expressed on the transfected cells induced the insulin production and/or promoted the growth in subclones of AR42J rat pancreatic cells. These results suggest that the membrane-anchored BTC can function as a juxtacrine factor in regulating the growth and differentiation of pancreatic endocrine cells.

Original languageEnglish
Pages (from-to)423-434
Number of pages12
JournalJournal of Cellular Biochemistry
Volume72
Issue number3
DOIs
Publication statusPublished - Mar 1 1999

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Keywords

  • Betacellulin
  • Isoforms
  • Juxtacrine stimulation
  • Membrane-anchored growth factor
  • Pancreatic cell differentiation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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