| http://purl.uniprot.org/citations/29487132 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29487132 | http://www.w3.org/2000/01/rdf-schema#comment | "The dopamine D2 receptor (D2R) is a G protein-coupled receptor (GPCR) that is critical for many central nervous system functions. The D2R carries out these functions by signaling through two transducers: G proteins and β-arrestins (βarrs). Selectively engaging either the G protein or βarr pathway may be a way to improve drugs targeting GPCRs. The current model of GPCR signal transduction posits a chain of events where G protein activation ultimately leads to βarr recruitment. GPCR kinases (GRKs), which are regulated by G proteins and whose kinase action facilitates βarr recruitment, bridge these pathways. Therefore, βarr recruitment appears to be intimately tied to G protein activation via GRKs. Here we sought to understand how GRK2 action at the D2R would be disrupted when G protein activation is eliminated and the effect of this on βarr recruitment. We used two recently developed biased D2R mutants that can preferentially interact either with G proteins or βarrs as well as a βarr-biased D2R ligand, UNC9994. With these functionally selective tools, we investigated the mechanism whereby the βarr-preferring D2R achieves βarr pathway activation in the complete absence of G protein activation. We describe how direct, G protein-independent recruitment of GRK2 drives interactions at the βarr-preferring D2R and also contributes to βarr recruitment at the WT D2R. Additionally, we found an additive interaction between the βarr-preferring D2R mutant and UNC9994. These results reveal that the D2R can directly recruit GRK2 without G protein activation and that this mechanism may have relevance to achieving βarr-biased signaling."xsd:string |
| http://purl.uniprot.org/citations/29487132 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra117.001300"xsd:string |
| http://purl.uniprot.org/citations/29487132 | http://purl.uniprot.org/core/author | "Caron M.G."xsd:string |
| http://purl.uniprot.org/citations/29487132 | http://purl.uniprot.org/core/author | "Ray C."xsd:string |
| http://purl.uniprot.org/citations/29487132 | http://purl.uniprot.org/core/author | "Peterson S.M."xsd:string |
| http://purl.uniprot.org/citations/29487132 | http://purl.uniprot.org/core/author | "Pack T.F."xsd:string |
| http://purl.uniprot.org/citations/29487132 | http://purl.uniprot.org/core/author | "Orlen M.I."xsd:string |
| http://purl.uniprot.org/citations/29487132 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29487132 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/29487132 | http://purl.uniprot.org/core/pages | "6161-6171"xsd:string |
| http://purl.uniprot.org/citations/29487132 | http://purl.uniprot.org/core/title | "The dopamine D2 receptor can directly recruit and activate GRK2 without G protein activation."xsd:string |
| http://purl.uniprot.org/citations/29487132 | http://purl.uniprot.org/core/volume | "293"xsd:string |
| http://purl.uniprot.org/citations/29487132 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29487132 |
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