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Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors

2016Journal article Open access
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dc.contributor.authorJiménez-Canino, Rubén
dc.contributor.authorFernandes, Miguel X.
dc.contributor.authorAlvarez de la Rosa, Diego
dc.date.accessioned2023-02-13T11:34:33Z
dc.date.available2023-02-13T11:34:33Z
dc.date.issued2016
dc.description.abstractPost-translational modification of steroid receptors allows fine-tuning different properties of this family of proteins, including stability, activation, or interaction with co-regulators. Recently, a novel effect of phosphorylation on steroid receptor biology was described. Phosphorylation of human mineralocor ticoid receptor (MR) on Ser-843, a residue placed on the ligand binding domain, lowers affinity for agonists, producing inhibi tion of gene transactivation. We now show that MR inhibition by phosphorylation occurs even at high agonist concentration, suggesting that phosphorylation may also impair coupling between ligand binding and receptor activation. Our results demonstrate that agonists are able to induce partial nuclear translocation of MR but fail to produce transactivation due at least in part to impaired co-activator recruitment. The inhibi tory effect of phosphorylation on MR acts in a dominant-nega tive manner, effectively amplifying its functional effect on gene transactivation.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJiménez-Canino, R., Fernandes, M. X., & Alvarez de la Rosa, D. (2016). Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors. Journal of Biological Chemistry, 291(36), 19068-19078.pt_PT
dc.identifier.doi10.1074/jbc.M116.718395pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.13/5029
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAldosteronept_PT
dc.subjectGene transcriptionpt_PT
dc.subjectGlucocorticoid receptorpt_PT
dc.subjectKidneypt_PT
dc.subjectMineralocorticoid receptorpt_PT
dc.subjectPhosphorylationpt_PT
dc.subjectSteroid hormone receptorpt_PT
dc.subjectCortisolpt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.titlePhosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptorspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage19078pt_PT
oaire.citation.issue36pt_PT
oaire.citation.startPage19068pt_PT
oaire.citation.titleJournal of Biological Chemistrypt_PT
oaire.citation.volume291pt_PT
person.familyNameFernandes
person.givenNameMiguel Xavier
person.identifier.ciencia-idED1D-3C7A-467C
person.identifier.orcid0000-0002-1840-616X
person.identifier.ridA-4373-2013
person.identifier.scopus-author-id35466972500
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication8dab9a0d-f44a-4d2d-b9b1-7b3145162ca3
relation.isAuthorOfPublication.latestForDiscovery8dab9a0d-f44a-4d2d-b9b1-7b3145162ca3

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