| Title: | Differential effects of RGS proteins on G alpha(q) and G alpha(11) activity |
| Author(s): | Ladds G; Goddard A; Hill C; Thornton S; Davey J; |
| Address: | "Division of Clinical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK. Graham.ladds@warwick.ac.uk" |
| DOI: | 10.1016/j.cellsig.2006.05.027 |
| ISSN/ISBN: | 0898-6568 (Print) 0898-6568 (Linking) |
| 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 G alpha(q) and G alpha(11) spontaneously activated the yeast pheromone-response pathway by a mechanism which required the formation of G alpha-GTP. This provided an assay for the specific activity of human RGS proteins. RGS1, RGS2, RGS3 and RGS4 inhibited the spontaneous activity of both G alpha(q) and G alpha(11) but, in contrast, RGS5 and RGS16 were much less effective against G alpha(11) than G alpha(q). Interestingly, RGS2 and RGS3 were able to inhibit signalling from the constitutively active G alpha(q)QL/G alpha(11)QL mutants, confirming the GAP-independent activity of these RGS proteins. To determine if the RGS-G alpha specificity was maintained under conditions of GPCR stimulation, minor modifications to the C-terminus of G alpha(q)/G alpha(11) enabled coupling to an endogenous receptor. RGS2 and RGS3 were effective inhibitors of both G alpha subunits even at high levels of receptor stimulation, emphasising their GAP-independent activity. At low levels of stimulation RGS5 and RGS16 retained their differential G alpha activity, further highlighting that RGS proteins can discriminate between two very closely related G alpha subunits" |
| Keywords: | "GTP-Binding Protein alpha Subunits, Gq-G11/genetics/*metabolism Humans Mutation Pheromones/metabolism Protein Subunits/genetics/metabolism RGS Proteins/genetics/*physiology Schizosaccharomyces/cytology/metabolism *Signal Transduction;" |
| Notes: | "MedlineLadds, Graham Goddard, Alan Hill, Claire Thornton, Steven Davey, John eng Research Support, Non-U.S. Gov't England 2006/07/18 Cell Signal. 2007 Jan; 19(1):103-13. doi: 10.1016/j.cellsig.2006.05.027. Epub 2006 Jun 7" |
