Switching heterotrimeric G protein subunits with a chemical dimerizer

Mateusz Putyrski, Carsten Schultz

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

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 Gα 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 Gα q, in full agreement with the InsP 3-Ca 2+ cross-coupling model of calcium oscillations. Rapamycin-induced translocation of wild-type Gα s to the plasma membrane results in elevated cAMP levels. Activation of rapamycin-inducible Gα s or Gβ 1γ 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.

Original languageEnglish (US)
Pages (from-to)1126-1133
Number of pages8
JournalChemistry and Biology
Volume18
Issue number9
DOIs
StatePublished - Sep 23 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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