Ra. Baumgartner et al., ENHANCEMENT OF TNF-ALPHA SYNTHESIS BY OVEREXPRESSION OF G(ALPHA-Z) INA MAST-CELL LINE, The Journal of immunology, 157(4), 1996, pp. 1625-1629
Ag stimulation of mast cells via the IgE receptor (Fc epsilon RI) elic
its production and release of numerous cytokines. This activation of F
c epsilon RI initiates various tyrosine kinase-dependent signaling cas
cades, which ultimately result in the de novo synthesis of cytokines,
To date, no heterotrimeric G proteins have been implicated in this pro
cess, Here we report that the alpha subunit of the heterotrimeric G pr
otein, G(2), can regulate production of the cytokine, TNF-alpha. The a
lpha subunit was overexpressed in a cultured mast cell line (RBL-2H3)
known to contain G(alpha z). In stimulated cells, overexpression of G(
alpha z) significantly enhanced the production of TNF-alpha. This effe
ct of G(alpha z) appeared to be restricted in that constitutive synthe
sis of the cytokine, TGF-beta, and Ag-stimulation of the phosphoinosit
ide-dependent secretory pathway were not significantly affected, Thus,
G(alpha z), a heterotrimeric G protein, appeared to modulate the stim
ulatory pathways for induction of TNF-alpha synthesis in RBL-2H3 cells
.