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Processing and juxtacrine activity of membrane‐anchored betacellulin
Author(s) -
Tada Hiroko,
Sasada Reiko,
Kawaguchi Yasuko,
Kojima Itaru,
Gullick William J.,
Salomon David S.,
Igarashi Koichi,
Seno Masaharu,
Yamada Hidenori
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990301)72:3<423::aid-jcb11>3.0.co;2-p
Subject(s) - juxtacrine signalling , microbiology and biotechnology , transfection , chinese hamster ovary cell , biology , cell culture , epidermal growth factor , autocrine signalling , genetics
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. J. Cell. Biochem. 72:423–434, 1999. © 1999 Wiley‐Liss, Inc.