期刊
CHEMISTRY & BIOLOGY
卷 18, 期 9, 页码 1126-1133出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2011.07.013
关键词
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资金
- Helmholtz Association (SBCancer)
- ESF
- DFG [Schu 943/8-1]
The selective manipulation of single intracellular-signaling events remains one of the key tasks when studying signaling networks. Here, we demonstrate for the first time the stimulation of FKBP fusions of various subunits of heterotrimeric G proteins by the simple addition of the chemical dimerizer rapamycin. Activation of constitutively active G alpha(q), but not its GDP-bound form, leads to sustained oscillations of intracellular calcium and myo-inositol 1,4,5-trisphosphate (InsP(3)) levels in HEK cells, independent of the activation of endogenous Gag, in full agreement with the InsP(3)-Ca2+ cross-coupling model of calcium oscillations. Rapamycin-induced translocation of wild-type Gas to the plasma membrane results in elevated cAMP levels. Activation of rapamycin-inducible G alpha(s) or G beta(1 gamma 2) evokes extensive modulation of ATP-induced calcium transients. The results demonstrate that inducible heterotrimeric G protein subunits will provide ways for dissecting G protein-coupled receptor signaling.
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