| http://purl.uniprot.org/citations/16407241 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16407241 | http://www.w3.org/2000/01/rdf-schema#comment | "There is considerable evidence for the role of carboxyl-terminal serines 355, 356, and 364 in G protein-coupled receptor kinase (GRK)-mediated phosphorylation and desensitization of beta(2)-adrenergic receptors (beta(2)ARs). In this study we used receptors in which these serines were changed to alanines (SA3) or to aspartic acids (SD3) to determine the role of these sites in beta-arrestin-dependent beta(2)AR internalization and desensitization. Coupling efficiencies for epinephrine activation of adenylyl cyclase were similar in wild-type and mutant receptors, demonstrating that the SD3 mutant did not drive constitutive GRK desensitization. Treatment of wild-type and mutant receptors with 0.3 nm isoproterenol for 5 min induced approximately 2-fold increases in the EC(50) for agonist activation of adenylyl cyclase, consistent with protein kinase A (PKA) site-mediated desensitization. When exposed to 1 mum isoproterenol to trigger GRK site-mediated desensitization, only wild-type receptors showed significant further desensitization. Using a phospho site-specific antibody, we determined that there is no requirement for these GRK sites in PKA-mediated phosphorylation at high agonist concentration. The rates of agonist-induced internalization of the SD3 and SA3 mutants were 44 and 13%, respectively, relative to that of wild-type receptors, but the SD3 mutant recruited enhanced green fluorescent protein (EGFP)-beta-arrestin 2 to the plasma membrane, whereas the SA3 mutant did not. EGFP-beta-Arrestin2 overexpression triggered a significant increase in the extent of SD3 mutant desensitization but had no effect on the desensitization of wild-type receptors or the SA3 mutant. Expression of a phosphorylation-independent beta-arrestin 1 mutant (R169E) significantly rescued the internalization defect of the SA3 mutant but inhibited the phosphorylation of serines 355 and 356 in wild-type receptors. Our data demonstrate that (i) the lack of GRK sites does not impair PKA site phosphorylation, (ii) the SD3 mutation inhibits GRK-mediated desensitization although it supports some agonist-induced beta-arrestin binding and receptor internalization, and (iii) serines 355, 356, and 364 play a pivotal role in the GRK-mediated desensitization, beta-arrestin binding, and internalization of beta(2)ARs."xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m500328200"xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/author | "Friedman J."xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/author | "Dai W."xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/author | "Tran T.M."xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/author | "Vaughan D.J."xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/author | "Clark R.B."xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/author | "Knoll B.J."xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/author | "Moore R.H."xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/author | "Millman E.E."xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/author | "Godines V."xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/pages | "7684-7692"xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/title | "Role of the G protein-coupled receptor kinase site serine cluster in beta2-adrenergic receptor internalization, desensitization, and beta-arrestin translocation."xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://purl.uniprot.org/core/volume | "281"xsd:string |
| http://purl.uniprot.org/citations/16407241 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16407241 |
| http://purl.uniprot.org/citations/16407241 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16407241 |
| http://purl.uniprot.org/uniprot/#_A2N4T7-mappedCitation-16407241 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16407241 |
| http://purl.uniprot.org/uniprot/#_B9EIS4-mappedCitation-16407241 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16407241 |
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| http://purl.uniprot.org/uniprot/#_O95098-mappedCitation-16407241 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16407241 |