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Differential effects of RGS proteins on Gαq and Gα11 activity
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Ladds, Graham, Goddard, Alan, Hill, Claire, Thornton, Steven and Davey, John (2006) Differential effects of RGS proteins on Gαq and Gα11 activity. Cellular Signalling, Vol.19 (No.1). pp. 103-113. doi:10.1016/j.cellsig.2006.05.027 ISSN 0898-6568.
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Official URL: http://dx.doi.org/10.1016/j.cellsig.2006.05.027
Abstract
Heterotrimeric G proteins play a pivotal role in GPCR signalling; they link receptors to intracellular
effectors and their inactivation by RGS proteins is a key factor in resetting the pathway following
stimulation. The precise GPCR:G protein:RGS combination determines the nature and duration of
the response. Investigating the activity of particular combinations is difficult in cells which contain
multiples of each component. We have therefore utilised a previously characterised yeast system to
express mammalian proteins in isolation. Human Gαq and Gα11 spontaneously activated the yeast
pheromone-response pathway by a mechanism which required the formation of Gα-GTP. This
provided an assay for the specific activity of human RGS proteins. RGS1, RGS2, RGS3 and RGS4
inhibited the spontaneous activity of both Gαq and Gα11 but, in contrast, RGS5 and RGS16 were
much less effective against Gα11 than Gαq. Interestingly, RGS2 and RGS3 were able to inhibit
signalling from the constitutively active Gαq
QL/Gα11
QL mutants, confirming the GAP-independent
activity of these RGS proteins. To determine if the RGS-Gα specificity was maintained under
conditions of GPCR stimulation, minor modifications to the C-terminus of Gαq/Gα11 enabled
coupling to an endogenous receptor. RGS2 and RGS3 were effective inhibitors of both Gα subunits
even at high levels of receptor stimulation, emphasising their GAP-independent activity. At low
levels of stimulation RGS5 and RGS16 retained their differential Gα activity, further highlighting
that RGS proteins can discriminate between two very closely related Gα subunits.
Item Type: | Journal Article | ||||
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Subjects: | R Medicine > R Medicine (General) | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
Library of Congress Subject Headings (LCSH): | G proteins | ||||
Journal or Publication Title: | Cellular Signalling | ||||
Publisher: | Elsevier | ||||
ISSN: | 0898-6568 | ||||
Official Date: | 7 June 2006 | ||||
Dates: |
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Volume: | Vol.19 | ||||
Number: | No.1 | ||||
Page Range: | pp. 103-113 | ||||
DOI: | 10.1016/j.cellsig.2006.05.027 | ||||
Status: | Peer Reviewed | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Description: | Version accepted by publisher (post-print, after peer review, before copy-editing). |
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Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), University Hospitals Coventry and Warwickshire NHS Trust |
Data sourced from Thomson Reuters' Web of Knowledge
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