| http://purl.uniprot.org/citations/18621717 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18621717 | http://www.w3.org/2000/01/rdf-schema#comment | "Beta-arrestins critically regulate G protein-coupled receptors (GPCRs), also known as seven-transmembrane receptors (7TMRs), both by inhibiting classical G protein signaling and by initiating distinct beta-arrestin-mediated signaling. The recent discovery of beta-arrestin-biased ligands and receptor mutants has allowed characterization of these independent "G protein-mediated" and "beta-arrestin-mediated" signaling mechanisms of 7TMRs. However, the molecular mechanisms underlying the dual functions of beta-arrestins remain unclear. Here, using an intramolecular BRET (bioluminescence resonance energy transfer)-based biosensor of beta-arrestin 2 and a combination of biased ligands and/or biased mutants of three different 7TMRs, we provide evidence that beta-arrestin can adopt multiple "active" conformations. Surprisingly, phosphorylation-deficient mutants of the receptors are also capable of directing similar conformational changes in beta-arrestin as is the wild-type receptor. This indicates that distinct receptor conformations induced and/or stabilized by different ligands can promote distinct and functionally specific conformations in beta-arrestin even in the absence of receptor phosphorylation. Our data thus highlight another interesting aspect of 7TMR signaling--i.e., functionally specific receptor conformations can be translated to downstream effectors such as beta-arrestins, thereby governing their functional specificity."xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0804246105"xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://purl.uniprot.org/core/author | "Lefkowitz R.J."xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://purl.uniprot.org/core/author | "Shukla A.K."xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://purl.uniprot.org/core/author | "Shenoy S.K."xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://purl.uniprot.org/core/author | "Whalen E.J."xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://purl.uniprot.org/core/author | "Violin J.D."xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://purl.uniprot.org/core/author | "Gesty-Palmer D."xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18621717 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://purl.uniprot.org/core/pages | "9988-9993"xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://purl.uniprot.org/core/title | "Distinct conformational changes in beta-arrestin report biased agonism at seven-transmembrane receptors."xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://purl.uniprot.org/core/volume | "105"xsd:string |
| http://purl.uniprot.org/citations/18621717 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18621717 |
| http://purl.uniprot.org/citations/18621717 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18621717 |
| http://purl.uniprot.org/uniprot/#_A8K4I6-mappedCitation-18621717 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18621717 |
| http://purl.uniprot.org/uniprot/#_K7ENA6-mappedCitation-18621717 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18621717 |
| http://purl.uniprot.org/uniprot/#_P32121-mappedCitation-18621717 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18621717 |
| http://purl.uniprot.org/uniprot/#_L8ECB1-mappedCitation-18621717 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18621717 |
| http://purl.uniprot.org/uniprot/#_Q59EM5-mappedCitation-18621717 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18621717 |
| http://purl.uniprot.org/uniprot/#_Q68DZ5-mappedCitation-18621717 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18621717 |
| http://purl.uniprot.org/uniprot/A8K4I6 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18621717 |
| http://purl.uniprot.org/uniprot/K7ENA6 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18621717 |
| http://purl.uniprot.org/uniprot/Q68DZ5 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18621717 |