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

Nature communications | 2011

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.

Pubmed ID: 22186894 RIS Download

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Associated grants

  • Agency: Austrian Science Fund FWF, Austria
    Id: P 22608
  • Agency: NIGMS NIH HHS, United States
    Id: U54 GM062114
  • Agency: CIHR, Canada
    Id: MOP-FRN-10501
  • Agency: CIHR, Canada
    Id: MOP-GMX-152556

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HEK293 (tool)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

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U2OS (tool)

RRID:CVCL_0042

Cell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)

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COS-7 (tool)

RRID:CVCL_0224

Cell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)

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