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RGS2 and RGS4 proteins: New modulators of the κ-opioid receptor signaling.
- Source :
-
Cellular Signalling . Jan2015, Vol. 27 Issue 1, p104-114. 11p. - Publication Year :
- 2015
-
Abstract
- Previous studies have shown that RGS4 associates with the C-termini of μ- and δ-opioid receptors in living cells and plays a key role in Gi/Go protein coupling selectivity and signalling of these receptors [12,20]. To deduce whether similar effects also occur for the κ-opioid receptor (κ-ΟR) and define the ability of members of the Regulators of G protein Signaling (RGS) of the B/R4 subfamily to interact with κ-ΟR subdomains we generated glutathione S-transferase fusion peptides encompassing the carboxyl-termini of κ-OR (κ-CT). Results from pull down experiments indicated that RGS2 and RGS4 directly interact within different domains of the κ-CT. Co-precipitation studies in living cells indicated that RGS2 and RGS4 associate with κ-ΟR constitutively and upon receptor activation and confer selectivity for coupling with a specific subset of G proteins. Expression of both members, RGS2 and/or RGS4, in 293 F cells attenuated κ-agonist mediated-adenylyl cyclase inhibition and extracellular signal regulated kinase (ERK1,2) phosphorylation with a different amplitude in their modulatory effect in κ-ΟR signaling. Our findings demonstrate that RGS2 and RGS4 are new interacting partners that play key roles in G protein coupling to negatively regulate κ-ΟR signaling. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08986568
- Volume :
- 27
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Cellular Signalling
- Publication Type :
- Academic Journal
- Accession number :
- 99793333
- Full Text :
- https://doi.org/10.1016/j.cellsig.2014.09.023