| http://purl.uniprot.org/citations/20861385 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20861385 | http://www.w3.org/2000/01/rdf-schema#comment | "Hyperexcitability of peripheral nociceptive pathways is often associated with inflammation and is an important mechanism underlying inflammatory pain. Here we describe a completely novel mechanism via which nociceptor G-protein-coupled receptor kinase 2 (GRK2) contributes to regulation of inflammatory hyperalgesia. We show that nociceptor GRK2 is downregulated during inflammation. In addition, we show for the first time that prostaglandin E2 (PGE2)-induced hyperalgesia is prolonged from <6 h in wild-type (WT) mice to 3 d in mice with low GRK2 in Nav1.8+ nociceptors (SNS-GRK2+/-mice). This prolongation of PGE2 hyperalgesia in SNS-GRK2+/-mice does not depend on changes in the sensitivity of the prostaglandin receptors because prolonged hyperalgesia also developed in response to 8-Br-cAMP. PGE2 or cAMP-induced hyperalgesia in WT mice is PKA dependent. However, PKA activity is not required for hyperalgesia in SNS-GRK2+/- mice. SNS-GRK2+/-mice developed prolonged hyperalgesia in response to the Exchange proteins directly activated by cAMP (Epac) activator 8-pCPT-2'-O-Me-cAMP (8-pCPT). Coimmunoprecipitation experiments showed that GRK2 binds to Epac1. In vitro, GRK2 deficiency increased 8-pCPT-induced activation of the downstream effector of Epac, Rap1, and extracellular signal-regulated kinase (ERK). In vivo, inhibition of MEK1 or PKCε prevented prolonged PGE2, 8-Br-cAMP, and 8-pCPT hyperalgesia in SNS-GRK2+/-mice. In conclusion, we discovered GRK2 as a novel Epac1-interacting protein. A reduction in the cellular level of GRK2 enhances activation of the Epac-Rap1 pathway. In vivo, low nociceptor GRK2 leads to prolonged inflammatory hyperalgesia via biased cAMP signaling from PKA to Epac-Rap1, ERK/PKCε pathways."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.3142-10.2010"xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/author | "Willemen H.L."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/author | "Wang H."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/author | "Wood J.N."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/author | "Eijkelkamp N."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/author | "Heijnen C.J."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/author | "Kavelaars A."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/author | "Zwartkruis F.J."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/author | "Dantzer R."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/author | "Kelley K.W."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/author | "Garza-Carbajal A."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/name | "J Neurosci"xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/pages | "12806-12815"xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/title | "Low nociceptor GRK2 prolongs prostaglandin E2 hyperalgesia via biased cAMP signaling to Epac/Rap1, protein kinase Cepsilon, and MEK/ERK."xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://purl.uniprot.org/core/volume | "30"xsd:string |
| http://purl.uniprot.org/citations/20861385 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20861385 |
| http://purl.uniprot.org/citations/20861385 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/20861385 |
| http://purl.uniprot.org/uniprot/#_A0A286YDA5-mappedCitation-20861385 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20861385 |
| http://purl.uniprot.org/uniprot/#_A0A286YDZ5-mappedCitation-20861385 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20861385 |
| http://purl.uniprot.org/uniprot/#_A0A286YE10-mappedCitation-20861385 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20861385 |
| http://purl.uniprot.org/uniprot/#_A0A0R5RP33-mappedCitation-20861385 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20861385 |
| http://purl.uniprot.org/uniprot/#_A0A0R5RP34-mappedCitation-20861385 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20861385 |