| http://purl.uniprot.org/citations/18353977 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18353977 | http://www.w3.org/2000/01/rdf-schema#comment | "Uncontrolled activation of the coagulation cascade after tissue injury has been implicated in both inflammation and tissue fibrosis. Thrombin exerts pluripotent cellular effects via its high-affinity receptor, proteinase-activated receptor-1 (PAR(1)) and signaling via Galpha(i/o), Galpha(q), or Galpha(12/13). Activation of PAR(1) on fibroblasts, a key effector cell in fibrosis, results in the induction of several mediators, including the potent monocyte and fibrocyte chemoattractant CCL2. The aim of this study was to identify the G protein and signaling pathway involved in PAR(1)-mediated CCL2 production and release. Using a novel PAR(1) antagonist that blocks the interaction between PAR(1) and Galpha(q), we report for the first time that PAR(1) coupling to Galpha(q) is essential for thrombin-induced CCL2 gene expression and protein release in murine lung fibroblasts. We further demonstrate that these effects are mediated via the cooperation between ERK1/2 and Rho kinase signaling pathways: a calcium-independent protein kinase C (PKC), c-Raf, and ERK1/2 pathway was found to mediate PAR(1)-induced CCL2 gene transcription, whereas a phospholipase C, calcium-dependent PKC, and Rho kinase pathway influences CCL2 protein release. We propose that targeting the interaction between PAR(1) and Galpha(q) may allow us to selectively interfere with PAR(1) proinflammatory and profibrotic signaling, while preserving the essential role of other PAR(1)-mediated cellular responses."xsd:string |
| http://purl.uniprot.org/citations/18353977 | http://purl.org/dc/terms/identifier | "doi:10.1091/mbc.e07-07-0720"xsd:string |
| http://purl.uniprot.org/citations/18353977 | http://purl.uniprot.org/core/author | "Deng X."xsd:string |
| http://purl.uniprot.org/citations/18353977 | http://purl.uniprot.org/core/author | "Gilchrist A."xsd:string |
| http://purl.uniprot.org/citations/18353977 | http://purl.uniprot.org/core/author | "Chambers R.C."xsd:string |
| http://purl.uniprot.org/citations/18353977 | http://purl.uniprot.org/core/author | "Scotton C.J."xsd:string |
| http://purl.uniprot.org/citations/18353977 | http://purl.uniprot.org/core/author | "Mercer P.F."xsd:string |
| http://purl.uniprot.org/citations/18353977 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18353977 | http://purl.uniprot.org/core/name | "Mol Biol Cell"xsd:string |
| http://purl.uniprot.org/citations/18353977 | http://purl.uniprot.org/core/pages | "2520-2533"xsd:string |
| http://purl.uniprot.org/citations/18353977 | http://purl.uniprot.org/core/title | "Thrombin induces fibroblast CCL2/JE production and release via coupling of PAR1 to Galphaq and cooperation between ERK1/2 and Rho kinase signaling pathways."xsd:string |
| http://purl.uniprot.org/citations/18353977 | http://purl.uniprot.org/core/volume | "19"xsd:string |
| http://purl.uniprot.org/citations/18353977 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18353977 |
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