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Reference: Stefan E, et al. (2011) PKA regulatory subunits mediate synergy among conserved G-protein-coupled receptor cascades. Nat Commun 2:598

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Abstract

G-protein-coupled receptors sense extracellular chemical or physical stimuli and transmit these signals to distinct trimeric G-proteins. Activated Galpha-proteins route signals to interconnected effector cascades, thus regulating thresholds, amplitudes and durations of signalling. Galphas- or Galphai-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 Galphas-coupled receptor cascades, the regulatory subunit type-II (RII) of protein kinase A undergoes adenosine 3'-5'-cyclic monophosphate (cAMP)-dependent binding to Galphai. Stimulation of a mammalian Galphai-coupled receptor and concomitant cAMP-RII binding to Galphai, augments the sensitivity, amplitude and duration of Galphai:betagamma 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 Galphas-coupled receptors controls the precision of adaptive responses of activated Galphai-coupled receptor cascades.

Reference Type
Journal Article
Authors
Stefan E, Malleshaiah MK, Breton B, Ear PH, Bachmann V, Beyermann M, Bouvier M, Michnick SW
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