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http://purl.uniprot.org/citations/27623777http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27623777http://www.w3.org/2000/01/rdf-schema#comment"The parathyroid hormone receptor 1 (PTH1R) is a member of family B of G-protein-coupled receptors (GPCRs), predominantly expressed in bone and kidney where it modulates extracellular Ca2+ homeostasis and bone turnover. It is well established that phosphorylation of GPCRs constitutes a key event in regulating receptor function by promoting arrestin recruitment and coupling to G-protein-independent signaling pathways. Mapping phosphorylation sites on PTH1R would provide insights into how phosphorylation at specific sites regulates cell signaling responses and also open the possibility of developing therapeutic agents that could target specific receptor functions. Here, we have used mass spectrometry to identify nine sites of phosphorylation in the C-terminal tail of PTH1R. Mutational analysis revealed identified two clusters of serine and threonine residues (Ser489-Ser495 and Ser501-Thr506) specifically responsible for the majority of PTH(1-34)-induced receptor phosphorylation. Mutation of these residues to alanine did not affect negatively on the ability of the receptor to couple to G-proteins or activate extracellular-signal-regulated kinase 1/2. Using fluorescence resonance energy transfer and bioluminescence resonance energy transfer to monitor PTH(1-34)-induced interaction of PTH1R with arrestin3, we show that the first cluster Ser489-Ser495 and the second cluster Ser501-Thr506 operated in concert to mediate both the efficacy and potency of ligand-induced arrestin3 recruitment. We further demonstrate that Ser503 and Thr504 in the second cluster are responsible for 70% of arrestin3 recruitment and are key determinants for interaction of arrestin with the receptor. Our data are consistent with the hypothesis that the pattern of C-terminal tail phosphorylation on PTH1R may determine the signaling outcome following receptor activation."xsd:string
http://purl.uniprot.org/citations/27623777http://purl.org/dc/terms/identifier"doi:10.1042/bcj20160740"xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/author"Bottrill A.R."xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/author"Prezeau L."xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/author"Tobin A.B."xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/author"Butcher A.J."xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/author"Krasel C."xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/author"Engel S."xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/author"Pin J.P."xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/author"Bunemann M."xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/author"Zindel D."xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/name"Biochem J"xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/pages"4173-4192"xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/title"Identification of key phosphorylation sites in PTH1R that determine arrestin3 binding and fine-tune receptor signaling."xsd:string
http://purl.uniprot.org/citations/27623777http://purl.uniprot.org/core/volume"473"xsd:string
http://purl.uniprot.org/citations/27623777http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27623777
http://purl.uniprot.org/citations/27623777http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27623777
http://purl.uniprot.org/uniprot/#_Q03431-mappedCitation-27623777http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27623777
http://purl.uniprot.org/uniprot/#_Q0VGD7-mappedCitation-27623777http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27623777
http://purl.uniprot.org/uniprot/#_Q71UK6-mappedCitation-27623777http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27623777
http://purl.uniprot.org/uniprot/Q03431http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/27623777
http://purl.uniprot.org/uniprot/Q0VGD7http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/27623777
http://purl.uniprot.org/uniprot/Q71UK6http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/27623777