Betacellulin (BTC), a member of the epidermal growth factor (EGF) family, is synthesized as a membrane-bound form which is cleaved to a released form. This represents the switching juxtacrine function of BTC to paracrine. To analyze the mechanism of cleavage, we established a series of recombinant cells that produced an alkaline phosphatase (ALP) fused to a part of membrane-bound BTC using Chinese hamster Ovary (CHO) cells and mouse fibroblast cell lines (A9 and Balb/c 3T3 A31). In CHO transfectants, about 90% of total ALP activity was retained on the cells, whereas A9 and Balb/c 3T3 A31 transfectants extensively secreted the ALP activity (about 40%). None of the stimulants, including a phorbor ester (PMA), A23187, retinoic acid, cAMP, cGMP, fibroblasl growth factor, EGF and BTC its self, enhanced the cleavage and release of ALP-BTC in these transfectants. These results suggest that the cleavage of BTC is regulated in different ways from those of other members of EGF-family, such as transforming growth factor a and heparin-binding EGF-like growth factor, whose cleavage are excellently stimulated with PMA.
|Publication status||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology