| http://purl.uniprot.org/citations/17038311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17038311 | http://www.w3.org/2000/01/rdf-schema#comment | "Parathyroid hormone (PTH) stimulates ERK1/2 through both G-protein signaling and beta-arrestin2-mediated internalization. Beta-arrestin may serve as a scaffold for c-Src. However, the molecular mechanisms for ERK1/2 activation by PTH remain unclear. By using a targeted mutagenesis approach, we investigated the PTH/PTH-related protein receptor (PTH1R) structural determinants for ERK1/2 activation and transcriptional activity in HEK-293 cells. First, ERK1/2 activation was inhibited by PTH1R mutations that specifically abrogate G(q)-protein kinase C signaling without a decrease in cAMP-protein kinase A. Second, PTH1R C-terminal mutations and/or deletions that prevent interaction with beta-arrestin inhibited ERK1/2 activation. Similar results were obtained in HEK-293 cells co-expressing wild-type PTH1R and a dominant-negative beta-arrestin2. Third, the c-Src inhibitor PP2 and a kinase-dead c-SrcK295M mutant co-expressed with wild-type PTH1R both inhibited ERK1/2 activation. Furthermore, c-Src co-precipitated with both PTH1R and beta-arrestin2 in response to PTH. Deleting the PTH1R-proximal C terminus abolished these interactions. However, the need for receptor interaction with beta-arrestin to co-precipitate Src and activate ERK1/2 was obviated by expressing a constitutively active c-SrcY527A mutant, suggesting direct binding of activated Src to PTH1R. Subsequently, we identified and mutated to alanine four proline-rich motifs in the PTH1R distal C terminus, which resulted in loss of both c-Src and arrestin co-precipitation and significantly decreased ERK1/2 activation. These data delineate the multiple PTH1R structural determinants for ERK1/2 activation and newly identify a unique mechanism involving proline-rich motifs in the receptor C terminus for reciprocal scaffolding of c-Src and beta-arrestin2 with a class II G-protein-coupled receptor."xsd:string |
| http://purl.uniprot.org/citations/17038311 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m606762200"xsd:string |
| http://purl.uniprot.org/citations/17038311 | http://purl.uniprot.org/core/author | "Caverzasio J."xsd:string |
| http://purl.uniprot.org/citations/17038311 | http://purl.uniprot.org/core/author | "Rey A."xsd:string |
| http://purl.uniprot.org/citations/17038311 | http://purl.uniprot.org/core/author | "Ferrari S.L."xsd:string |
| http://purl.uniprot.org/citations/17038311 | http://purl.uniprot.org/core/author | "Rizzoli R."xsd:string |
| http://purl.uniprot.org/citations/17038311 | http://purl.uniprot.org/core/author | "Manen D."xsd:string |
| http://purl.uniprot.org/citations/17038311 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/17038311 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/17038311 | http://purl.uniprot.org/core/pages | "38181-38188"xsd:string |
| http://purl.uniprot.org/citations/17038311 | http://purl.uniprot.org/core/title | "Proline-rich motifs in the parathyroid hormone (PTH)/PTH-related protein receptor C terminus mediate scaffolding of c-Src with beta-arrestin2 for ERK1/2 activation."xsd:string |
| http://purl.uniprot.org/citations/17038311 | http://purl.uniprot.org/core/volume | "281"xsd:string |
| http://purl.uniprot.org/citations/17038311 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17038311 |
| http://purl.uniprot.org/citations/17038311 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/17038311 |
| http://purl.uniprot.org/uniprot/#_A8K4I6-mappedCitation-17038311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17038311 |
| http://purl.uniprot.org/uniprot/#_Q14925-mappedCitation-17038311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17038311 |
| http://purl.uniprot.org/uniprot/#_Q03431-mappedCitation-17038311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17038311 |
| http://purl.uniprot.org/uniprot/#_K7ENA6-mappedCitation-17038311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17038311 |
| http://purl.uniprot.org/uniprot/#_P32121-mappedCitation-17038311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17038311 |
| http://purl.uniprot.org/uniprot/#_L8ECB1-mappedCitation-17038311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17038311 |
| http://purl.uniprot.org/uniprot/#_P12931-mappedCitation-17038311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17038311 |
| http://purl.uniprot.org/uniprot/#_Q59EM5-mappedCitation-17038311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17038311 |
| http://purl.uniprot.org/uniprot/#_Q0VGD7-mappedCitation-17038311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17038311 |
| http://purl.uniprot.org/uniprot/#_Q68DZ5-mappedCitation-17038311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17038311 |