| http://purl.uniprot.org/citations/26987903 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26987903 | http://www.w3.org/2000/01/rdf-schema#comment | "Estrogen exerts many effects on the vascular endothelium. Calmodulin (CaM) is the transducer of Ca(2+) signals and is a limiting factor in cardiovascular tissues. It is unknown whether and how estrogen modifies endothelial functions via the network of CaM-dependent proteins. Here we show that 17β-estradiol (E2) up-regulates total CaM level in endothelial cells. Concurrent measurement of Ca(2+) and Ca(2+)-CaM indicated that E2 also increases free Ca(2+)-CaM. Pharmacological studies, gene silencing, and receptor expression-specific cell studies indicated that the G protein-coupled estrogen receptor 1 (GPER/GPR30) mediates these effects via transactivation of EGFR and subsequent MAPK activation. The outcomes were then examined on four distinct members of the intracellular CaM target network, including GPER/GPR30 itself and estrogen receptor α, the plasma membrane Ca(2+)-ATPase (PMCA), and endothelial nitric-oxide synthase (eNOS). E2 substantially increases CaM binding to estrogen receptor α and GPER/GPR30. Mutations that reduced CaM binding to GPER/GPR30 in separate binding domains do not affect GPER/GPR30-Gβγ preassociation but decrease GPER/GPR30-mediated ERK1/2 phosphorylation. E2 increases CaM-PMCA association, but the expected stimulation of Ca(2+) efflux is reversed by E2-stimulated tyrosine phosphorylation of PMCA. These effects sustain Ca(2+) signals and promote Ca(2+)-dependent CaM interactions with other CaM targets. Consequently, E2 doubles CaM-eNOS interaction and also promotes dual phosphorylation of eNOS at Ser-617 and Ser-1179. Calculations using in-cell and in vitro data revealed substantial individual and combined contribution of these effects to total eNOS activity. Taken together, E2 generates a feedforward loop via GPER/GPR30, which enhances Ca(2+)/CaM signals and functional linkage in the endothelial CaM target network."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m115.697334"xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/author | "Tran P."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/author | "Francis S."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/author | "Giles J."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/author | "Tran Q.K."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/author | "Burgard M.A."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/author | "Firkins R."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/author | "Gebert-Oberle B."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/author | "Jasurda J."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/author | "Matnishian V."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/author | "VerMeer M."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/pages | "10805-10823"xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/title | "Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-coupled Estrogen Receptor 1."xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://purl.uniprot.org/core/volume | "291"xsd:string |
| http://purl.uniprot.org/citations/26987903 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26987903 |
| http://purl.uniprot.org/citations/26987903 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26987903 |
| http://purl.uniprot.org/uniprot/#_P63092-mappedCitation-26987903 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26987903 |
| http://purl.uniprot.org/uniprot/#_O14775-mappedCitation-26987903 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26987903 |
| http://purl.uniprot.org/uniprot/#_P16520-mappedCitation-26987903 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26987903 |
| http://purl.uniprot.org/uniprot/#_P50150-mappedCitation-26987903 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26987903 |
| http://purl.uniprot.org/uniprot/#_P50151-mappedCitation-26987903 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26987903 |