Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors
Autor(a) principal: | |
---|---|
Data de Publicação: | 2016 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.13/5029 |
Resumo: | Post-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. |
id |
RCAP_7701978b9f8d9bc41f5dc2fb5bce2f12 |
---|---|
oai_identifier_str |
oai:digituma.uma.pt:10400.13/5029 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptorsAldosteroneGene transcriptionGlucocorticoid receptorKidneyMineralocorticoid receptorPhosphorylationSteroid hormone receptorCortisol.Faculdade de Ciências Exatas e da EngenhariaPost-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.ElsevierDigitUMaJiménez-Canino, RubénFernandes, Miguel X.Alvarez de la Rosa, Diego2023-02-13T11:34:33Z20162016-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.13/5029engJiménez-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), 19068-19078.10.1074/jbc.M116.718395info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-12T05:24:12Zoai:digituma.uma.pt:10400.13/5029Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:46:58.447485Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors |
title |
Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors |
spellingShingle |
Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors Jiménez-Canino, Rubén Aldosterone Gene transcription Glucocorticoid receptor Kidney Mineralocorticoid receptor Phosphorylation Steroid hormone receptor Cortisol . Faculdade de Ciências Exatas e da Engenharia |
title_short |
Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors |
title_full |
Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors |
title_fullStr |
Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors |
title_full_unstemmed |
Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors |
title_sort |
Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors |
author |
Jiménez-Canino, Rubén |
author_facet |
Jiménez-Canino, Rubén Fernandes, Miguel X. Alvarez de la Rosa, Diego |
author_role |
author |
author2 |
Fernandes, Miguel X. Alvarez de la Rosa, Diego |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
DigitUMa |
dc.contributor.author.fl_str_mv |
Jiménez-Canino, Rubén Fernandes, Miguel X. Alvarez de la Rosa, Diego |
dc.subject.por.fl_str_mv |
Aldosterone Gene transcription Glucocorticoid receptor Kidney Mineralocorticoid receptor Phosphorylation Steroid hormone receptor Cortisol . Faculdade de Ciências Exatas e da Engenharia |
topic |
Aldosterone Gene transcription Glucocorticoid receptor Kidney Mineralocorticoid receptor Phosphorylation Steroid hormone receptor Cortisol . Faculdade de Ciências Exatas e da Engenharia |
description |
Post-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. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016 2016-01-01T00:00:00Z 2023-02-13T11:34:33Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.13/5029 |
url |
http://hdl.handle.net/10400.13/5029 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Jiménez-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. 10.1074/jbc.M116.718395 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799130940972204032 |