N. Hirasawa et al., ROLE OF PHOSPHATIDYLINOSITOL 3-KINASE IN DEGRANULATION INDUCED BY IGE-DEPENDENT AND IGE-INDEPENDENT MECHANISMS IN RAT BASOPHILIC RBL-2H3(ML)-CELLS, Cellular signalling, 9(3-4), 1997, pp. 305-310
We have examined the role of phosphatidylinositol 3-kinase (PI3-kinase
) in the degranulation induced by the antigen, an IgE-dependent stimul
ant, and by carbachol and thapsigargin, IgE-independent stimulants, in
the muscarine ml receptor-transfected mast cell line RBL-2H3 (ml) cel
ls. These stimulants commonly increased PI3-kinase activity in the ant
i-phosphotyrosine immunoprecipitate. The PI3-kinase inhibitors wortman
nin and LY294002 inhibited the degranulation induced by these stimulan
ts. The membrane ruffling induced by the antigen or carbachol was also
inhibited by wortmannin. In contrast, thapsigargin induced by membran
e ruffling but induced microspikes, which was not affected by wortmann
in. In the permeabilized RBL-2H3 (mi) cells, wortmannin inhibited the
GTP gamma S-induced membrane ruffling without inhibiting the GTP gamma
S-induced degranulation. These findings suggest that PI3-kinase is in
volved not only in IgE-dependent degranulation but also in IgE-indepen
dent degranulation, and that the GTP gamma S-sensitive protein at the
downstream of PI3-kinase is responsible for the degranulation but not
for the membrane ruffling. (C) 1997 Elsevier Science Inc.