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Nat Commun

Title:		PKA regulatory subunits mediate synergy among conserved G-protein-coupled receptor cascades
Author(s):		Stefan E; Malleshaiah MK; Breton B; Ear PH; Bachmann V; Beyermann M; Bouvier M; Michnick SW;
Address:		"Institute of Biochemistry and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria. eduard.stefan@uibk.ac.at"
Journal Title:		Nat Commun
Year:		2011
Volume:		20111220
Issue:
Page Number:		598 -
DOI:		10.1038/ncomms1605
ISSN/ISBN:		2041-1723 (Electronic) 2041-1723 (Linking)
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"
Keywords:		"Adaptation, Physiological/*genetics Cloning, Molecular Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinase Type II/genetics/*metabolism Escherichia coli GTP-Binding Protein alpha Subunits/genetics/metabolism Gene Expression Regulation, Fungal/*physi;"
Notes:		"MedlineStefan, Eduard Malleshaiah, Mohan K Breton, Billy Ear, Po Hien Bachmann, Verena Beyermann, Michael Bouvier, Michel Michnick, Stephen W eng P 22608/FWF_/Austrian Science Fund FWF/Austria U54 GM062114/GM/NIGMS NIH HHS/ MOP-FRN-10501/CAPMC/CIHR/Canada MOP-GMX-152556/CAPMC/CIHR/Canada Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2011/12/22 Nat Commun. 2011 Dec 20; 2:598. doi: 10.1038/ncomms1605"