| http://purl.uniprot.org/citations/11773440 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/11773440 | http://www.w3.org/2000/01/rdf-schema#comment | "Estrogen triggers rapid yet transient activation of the MAPKs, extracellular signal-regulated kinase (Erk)-1 and Erk-2. We have reported that this estrogen action requires the G protein-coupled receptor, GPR30, and occurs via Gbetagamma-subunit protein-dependent transactivation of the epidermal growth factor (EGF) receptor through the release of pro-heparan-bound EGF from the cell surface. Here we investigate the mechanism by which Erk-1/-2 activity is rapidly restored to basal levels after estrogen stimulation. Evidence is provided that attenuation of Erk-1/-2 activity by estrogen occurs via GPR30-dependent stimulation of adenylyl cyclase and cAMP-dependent signaling that results in Raf-1 inactivation. We show that 17beta-E2 represses EGF-induced activation of the Raf-to-Erk pathway in human breast carcinoma cells that express GPR30, including MCF-7 and SKBR3 cells which express both or neither, ER, respectively. MDA-MB-231 cells, which express ERbeta, but not ERalpha, and low levels of GPR30 protein, are unable to stimulate adenylyl cyclase or promote estrogen-mediated blockade of EGF-induced activation of Erk-1/-2. Pretreatment of MDA-MB-231 cells with cholera toxin, which ADP-ribosylates and activates Galphas subunit proteins, results in G protein-coupled receptor (GPCR)-independent adenylyl cyclase activity and suppression of EGF-induced Erk-1/-2 activity. Transfection of GPR30 into MDA-MB-231 cells restores their ability to stimulate adenylyl cyclase and attenuate EGF-induced activation of Erk-1/-2 by estrogen. Moreover, GPR30-dependent, cAMP-mediated attenuation of EGF-induced Erk-1/-2 activity was achieved by ER antagonists such as tamoxifen or ICI 182, 780; yet not by 17alpha-E2 or progesterone. Thus, our data delineate a novel mechanism, requiring GPR30 and estrogen, that acts to regulate Erk-1/-2 activity via an inhibitory signal mediated by cAMP. Coupled with our prior findings, these current data imply that estrogen balances Erk-1/-2 activity through a single GPCR via two distinct G protein-dependent signaling pathways that have opposing effects on the EGF receptor-to-MAPK pathway."xsd:string |
| http://purl.uniprot.org/citations/11773440 | http://purl.org/dc/terms/identifier | "doi:10.1210/mend.16.1.0758"xsd:string |
| http://purl.uniprot.org/citations/11773440 | http://purl.uniprot.org/core/author | "Filardo E.J."xsd:string |
| http://purl.uniprot.org/citations/11773440 | http://purl.uniprot.org/core/author | "Quinn J.A."xsd:string |
| http://purl.uniprot.org/citations/11773440 | http://purl.uniprot.org/core/author | "Bland K.I."xsd:string |
| http://purl.uniprot.org/citations/11773440 | http://purl.uniprot.org/core/author | "Frackelton A.R. Jr."xsd:string |
| http://purl.uniprot.org/citations/11773440 | http://purl.uniprot.org/core/date | "2002"xsd:gYear |
| http://purl.uniprot.org/citations/11773440 | http://purl.uniprot.org/core/name | "Mol Endocrinol"xsd:string |
| http://purl.uniprot.org/citations/11773440 | http://purl.uniprot.org/core/pages | "70-84"xsd:string |
| http://purl.uniprot.org/citations/11773440 | http://purl.uniprot.org/core/title | "Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis."xsd:string |
| http://purl.uniprot.org/citations/11773440 | http://purl.uniprot.org/core/volume | "16"xsd:string |
| http://purl.uniprot.org/citations/11773440 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/11773440 |
| http://purl.uniprot.org/citations/11773440 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/11773440 |
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| http://purl.uniprot.org/uniprot/#_P50151-mappedCitation-11773440 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11773440 |
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| http://purl.uniprot.org/uniprot/#_P62873-mappedCitation-11773440 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/11773440 |