Tyrosine kinase-dependent phosphatidylinositol turnover and functional responses in the FcεR1 signalling pathway

Abstract In RBL-2H3 rat basophilic leukemia cells, FceR1 crosslinking by multivalent antigen stimulates phosphatidylinositol (PI) turnover and Ca 2+ influx and causes functional responses that include secretion, membrane ruffling and actin polymerization. Here, we show that the tyrosine kinase inhibitor, genistein, inhibits antigen-induced PI turnover, determined from assays of 1,4,5-inositol trisphosphate production, and impairs receptor-mediated secretion, ruffling and actin polymerization. Genistein has little effect on several functional responses to stimuli that bypass PI hydrolysis (ionomycininduced secretion, phorbol ester-induced ruffling) but it inhibits phorbol ester-induced actin polymerization. These data implicate a common tyrosine kinase-dependent event, most likely the activation of phospholipase Cγ, in the FceR1-mediated stimulation of PI turnover, secretion and ruffling. There may be additional tyrosine kinase-mediated events in the actin assembly pathway.