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RGS2 and RGS4 proteins: New modulators of the κ-opioid receptor signaling.

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 293F 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.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Papakonstantinou MP,Karoussiotis C,Georgoussi Z

doi

10.1016/j.cellsig.2014.09.023

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

104-14

issue

1

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(14)00327-1

journal_volume

27

pub_type

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