| http://purl.uniprot.org/citations/23775075 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23775075 | http://www.w3.org/2000/01/rdf-schema#comment | "There is considerable evidence to suggest that drug actions at the κ-opioid receptor (KOR) may represent a means to control pain perception and modulate reward thresholds. As a G protein-coupled receptor (GPCR), the activation of KOR promotes Gαi/o protein coupling and the recruitment of β-arrestins. It has become increasingly evident that GPCRs can transduce signals that originate independently via G protein pathways and β-arrestin pathways; the ligand-dependent bifurcation of such signaling is referred to as "functional selectivity" or "signaling bias." Recently, a KOR agonist, 6'-guanidinonaltrindole (6'-GNTI), was shown to display bias toward the activation of G protein-mediated signaling over β-arrestin2 recruitment. Therefore, we investigated whether such ligand bias was preserved in striatal neurons. Although the reference KOR agonist U69,593 induces the phosphorylation of ERK1/2 and Akt, 6'-GNTI only activates the Akt pathway in striatal neurons. Using pharmacological tools and β-arrestin2 knock-out mice, we show that KOR-mediated ERK1/2 phosphorylation in striatal neurons requires β-arrestin2, whereas Akt activation depends upon G protein signaling. These findings reveal a point of KOR signal bifurcation that can be observed in an endogenous neuronal setting and may prove to be an important indicator when developing biased agonists at the KOR."xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m113.476234"xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://purl.uniprot.org/core/author | "Zhou L."xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://purl.uniprot.org/core/author | "Bohn L.M."xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://purl.uniprot.org/core/author | "Schmid C.L."xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://purl.uniprot.org/core/author | "Streicher J.M."xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://purl.uniprot.org/core/author | "Groer C.E."xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://purl.uniprot.org/core/author | "Munro T.A."xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23775075 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://purl.uniprot.org/core/pages | "22387-22398"xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://purl.uniprot.org/core/title | "Functional selectivity of 6'-guanidinonaltrindole (6'-GNTI) at kappa-opioid receptors in striatal neurons."xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://purl.uniprot.org/core/volume | "288"xsd:string |
| http://purl.uniprot.org/citations/23775075 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23775075 |
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