| http://purl.uniprot.org/citations/22089237 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22089237 | http://www.w3.org/2000/01/rdf-schema#comment | "We previously identified a naturally occurring human SNP, G247R, in the third intracellular loop of the α(1a)-adrenergic receptor (α(1a)-247R) and demonstrated that constitutive expression of α(1a)-247R results in twofold increased cell proliferation compared with WT. In the present study we elucidate molecular mechanisms and signal transduction pathways responsible for increased cell proliferation unique to α(1a)-247R, but not α(1a)-WT, α(1b), or α(1d)AR subtypes. We show that elevated levels of matrix metalloproteinase-7 (MMP7) and a disintegrin and metalloproteinase-12 (ADAM12) in α(1a)-247R-expressing cells are responsible for EGF receptor (EGFR) transactivation, downstream ERK activation, and increased cell proliferation; this pathway is confirmed using MMP, EGFR, and ERK inhibitors. We demonstrate that EGFR transactivation and downstream ERK activation depends on increased shedding of heparin-binding EGF. Finally, we demonstrate that knockdown of MMP7 or β-arrestin1 by shRNAs results in attenuation of proliferation of cells expressing α(1a)-247R. Importantly, accelerated cell proliferation triggered by the α(1a)-247R is serum- and agonist-independent, providing unique evidence for constitutive active coupling to the β-arrestin1/MMP/EGFR transactivation pathway by any G protein-coupled receptor. These findings raise the possibility of a previously unexplored mechanism for sympathetically mediated human hypertension triggered by a naturally occurring human genetic variant."xsd:string |
| http://purl.uniprot.org/citations/22089237 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1116271108"xsd:string |
| http://purl.uniprot.org/citations/22089237 | http://purl.uniprot.org/core/author | "Schwinn D.A."xsd:string |
| http://purl.uniprot.org/citations/22089237 | http://purl.uniprot.org/core/author | "Yarov-Yarovoy V."xsd:string |
| http://purl.uniprot.org/citations/22089237 | http://purl.uniprot.org/core/author | "Parks W.C."xsd:string |
| http://purl.uniprot.org/citations/22089237 | http://purl.uniprot.org/core/author | "Oganesian A."xsd:string |
| http://purl.uniprot.org/citations/22089237 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/22089237 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/22089237 | http://purl.uniprot.org/core/pages | "19796-19801"xsd:string |
| http://purl.uniprot.org/citations/22089237 | http://purl.uniprot.org/core/title | "Constitutive coupling of a naturally occurring human alpha1a-adrenergic receptor genetic variant to EGFR transactivation pathway."xsd:string |
| http://purl.uniprot.org/citations/22089237 | http://purl.uniprot.org/core/volume | "108"xsd:string |
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