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http://purl.uniprot.org/citations/11350956http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11350956http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11350956http://www.w3.org/2000/01/rdf-schema#comment"11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2 has been considered to protect the mineralocorticoid receptor (MR) by converting 11beta-hydroxyglucocorticoids into their inactive 11-keto forms, thereby providing specificity to the MR for aldosterone. To investigate the functional protection of the MR by 11beta-HSD2, we coexpressed epitope-tagged MR and 11beta-HSD2 in HEK-293 cells lacking 11beta-HSD2 activity and analyzed their subcellular localization by fluorescence microscopy. When expressed alone in the absence of hormones, the MR was both cytoplasmic and nuclear. However, when coexpressed with 11beta-HSD2, the MR displayed a reticular distribution pattern, suggesting association with 11beta-HSD2 at the endoplasmic reticulum membrane. The endoplasmic reticulum membrane localization of the MR was observed upon coexpression only with 11beta-HSD2, but not with 11beta-HSD1 or other steroid-metabolizing enzymes. Aldosterone induced rapid nuclear translocation of the MR, whereas moderate cortisol concentrations (10-200 nm) did not activate the receptor, due to 11beta-HSD2-dependent oxidation to cortisone. Compromised 11beta-HSD2 activity (due to genetic mutations, the presence of inhibitors, or saturating cortisol concentrations) led to cortisol-induced nuclear accumulation of the MR. Surprisingly, the 11beta-HSD2 product cortisone blocked the aldosterone-induced MR activation by a strictly 11beta-HSD2-dependent mechanism. Our results provide evidence that 11beta-HSD2, besides inactivating 11beta-hydroxyglucocorticoids, functionally interacts with the MR and directly regulates the magnitude of aldosterone-induced MR activation."xsd:string
http://purl.uniprot.org/citations/11350956http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m100374200"xsd:string
http://purl.uniprot.org/citations/11350956http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m100374200"xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/author"Arnold P."xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/author"Arnold P."xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/author"Odermatt A."xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/author"Odermatt A."xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/author"Frey F.J."xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/author"Frey F.J."xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/date"2001"xsd:gYear
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/date"2001"xsd:gYear
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/pages"28484-28492"xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/pages"28484-28492"xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/title"The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2."xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/title"The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2."xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/volume"276"xsd:string
http://purl.uniprot.org/citations/11350956http://purl.uniprot.org/core/volume"276"xsd:string
http://purl.uniprot.org/citations/11350956http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/11350956
http://purl.uniprot.org/citations/11350956http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/11350956
http://purl.uniprot.org/citations/11350956http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/11350956
http://purl.uniprot.org/citations/11350956http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/11350956