Enhancement of fibroblast growth factor-induced diacylglycerol formation and protein kinase C activation by colon tumor-promoting bile acid in Swiss 3T3 cells. Different modes of action between bile acid and phorbol ester.
A small amount (50-200 microM) of deoxycholate (DOC), a colon tumor-promoting bile acid, did not show a direct effect on protein kinase C activity in a cell-free system, but enhanced fibroblast growth factor (FGF)-induced diacylglycerol formation and protein kinase C activation in Swiss 3T3 cells. DOC potentiated both reactions induced by submaximal doses of FGF but showed little effect on the maximal levels of the reactions. DOC alone was inactive in eliciting both reactions in the absence of FGF. DOC did not affect the binding of FGF to the cells. Since it has been described that diacylglycerol serves as a messenger for the activation of protein kinase C in the action of FGF in Swiss 3T3 cells [(1985) FEBS Lett. 191, 205-210], these results suggest that a small amount of DOC increases the sensitivity to FGF of diacylglycerol formation and thereby potentiates protein kinase C activation in this cell line. This action of DOC was in marked contrast to that of 12-O-tetradecanoylphorbol-13-acetate, a potent tumor-promoting phorbol ester, which directly activated protein kinase C in cell-free and intact cell systems.
D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D003110:Colonic Neoplasms / Q000139:chemically induced; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004075:Diglycerides / Q000096:biosynthesis*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005989:Glycerides / Q000096:biosynthesis*; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D005989:Glycerides; D003840:Deoxycholic Acid; D005346:Fibroblast Growth Factors; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate