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Nat Commun. 2011 Dec 20;2:598. doi: 10.1038/ncomms1605.

PKA regulatory subunits mediate synergy among conserved G-protein-coupled receptor cascades.

Author information

1
Institute of Biochemistry and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria. eduard.stefan@uibk.ac.at

Abstract

G-protein-coupled receptors sense extracellular chemical or physical stimuli and transmit these signals to distinct trimeric G-proteins. Activated Gα-proteins route signals to interconnected effector cascades, thus regulating thresholds, amplitudes and durations of signalling. Gαs- or Gαi-coupled receptor cascades are mechanistically conserved and mediate many sensory processes, including synaptic transmission, cell proliferation and chemotaxis. Here we show that a central, conserved component of Gαs-coupled receptor cascades, the regulatory subunit type-II (RII) of protein kinase A undergoes adenosine 3'-5'-cyclic monophosphate (cAMP)-dependent binding to Gαi. Stimulation of a mammalian Gαi-coupled receptor and concomitant cAMP-RII binding to Gαi, augments the sensitivity, amplitude and duration of Gαi:βγ activity and downstream mitogen-activated protein kinase signalling, independent of protein kinase A kinase activity. The mechanism is conserved in budding yeast, causing nutrient-dependent modulation of a pheromone response. These findings suggest a direct mechanism by which coincident activation of Gαs-coupled receptors controls the precision of adaptive responses of activated Gαi-coupled receptor cascades.

PMID:
22186894
PMCID:
PMC3247815
DOI:
10.1038/ncomms1605
[Indexed for MEDLINE]
Free PMC Article

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