Journal article
PKA regulatory subunits mediate synergy among conserved G-protein-coupled receptor cascades
Nature communications, Vol.2(1), pp.598-598
12/01/2011
DOI: 10.1038/ncomms1605
PMCID: PMC3247815
PMID: 22186894
Abstract
G-protein-coupled receptors sense extracellular chemical or physical stimuli and transmit these signals to distinct trimeric G-proteins. Activated G a-proteins route signals to interconnected effector cascades, thus regulating thresholds, amplitudes and durations of signalling. G a s-or G a i-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 G alpha s-coupled receptor cascades, the regulatory subunit type-II (RII) of protein kinase A undergoes adenosine 3'-5'-cyclic monophosphate ( cAMP)dependent binding to G alpha i. Stimulation of a mammalian G alpha i-coupled receptor and concomitant cAMP-RII binding to G alpha i, augments the sensitivity, amplitude and duration of G alpha i: beta gamma. 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 fi ndings suggest a direct mechanism by which coincident activation of G alpha s-coupled receptors controls the precision of adaptive responses of activated G alpha i-coupled receptor cascades.
Details
- Title: Subtitle
- PKA regulatory subunits mediate synergy among conserved G-protein-coupled receptor cascades
- Creators
- Eduard Stefan - Universität InnsbruckMohan K. Malleshaiah - Université de MontréalBilly Breton - Institute for Research in Immunology and CancerPo Hien Ear - Université de MontréalVerena Bachmann - Universität InnsbruckMichael Beyermann - Leibniz-Forschungsinstitut für Molekulare PharmakologieMichel Bouvier - Institute for Research in Immunology and CancerStephen W. Michnick - Université de Montréal
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.2(1), pp.598-598
- Publisher
- Springer Nature
- DOI
- 10.1038/ncomms1605
- PMID
- 22186894
- PMCID
- PMC3247815
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Number of pages
- 10
- Grant note
- U54GM062114 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) MOP-GMX-152556; MOP-FRN-10501 / Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR) University of Innsbruck P22608 / Austrian Science Fund Grant P 22608 / Austrian Science Fund (FWF)
- Language
- English
- Date published
- 12/01/2011
- Academic Unit
- Surgery
- Record Identifier
- 9984322794102771
Metrics
4 Record Views