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A physiologically required G protein-coupled receptor (GPCR)-regulator of G protein signaling (RGS) interaction that compartmentalizes RGS activity
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Croft, Wayne D., Hills, Claire E., McCann, Eilish Clare, Bond, Michael, Esparza Franco, Manuel A., Bennett, Jeanette, Rand, D. A. (David A.), Davey, John and Ladds, Graham (2013) A physiologically required G protein-coupled receptor (GPCR)-regulator of G protein signaling (RGS) interaction that compartmentalizes RGS activity. Journal of Biological Chemistry, Volume 288 (Number 38). pp. 27327-27342. doi:10.1074/jbc.M113.497826 ISSN 0021-9258.
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Official URL: http://dx.doi.org/10.1074/jbc.M113.497826
Abstract
G protein-coupled receptors (GPCRs) can interact with regulator of G protein signaling (RGS) proteins. However, the effects of such interactions on signal transduction and their physiological relevance have been largely undetermined. Ligand-bound GPCRs initiate by promoting exchange of GDP for GTP on the Gα subunit of heterotrimeric G proteins. Signaling is terminated by hydrolysis of GTP to GDP through intrinsic GTPase activity of the Gα subunit, a reaction catalyzed by RGS proteins. Using yeast as a tool to study GPCR signaling in isolation, we define an interaction between the cognate GPCR (Mam2) and RGS (Rgs1), mapping the interaction domains. This reaction tethers Rgs1 at the plasma membrane and is essential for physiological signaling response. In vivo quantitative data inform the development of a kinetic model of the GTPase cycle, which extends previous attempts by including GPCR-RGS interactions. In vivo and in silico data confirm that GPCR-RGS interactions can impose an additional layer of regulation through mediating RGS subcellular localization to compartmentalize RGS activity within a cell, thus highlighting their importance as potential targets to modulate GPCR signaling pathways.
| Item Type: | Journal Article | ||||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Journal of Biological Chemistry | ||||||
| Publisher: | American Society for Biochemistry and Molecular Biology | ||||||
| ISSN: | 0021-9258 | ||||||
| Official Date: | 30 July 2013 | ||||||
| Dates: |
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| Volume: | Volume 288 | ||||||
| Number: | Number 38 | ||||||
| Page Range: | pp. 27327-27342 | ||||||
| DOI: | 10.1074/jbc.M113.497826 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Restricted or Subscription Access |
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