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Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors
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Orientador(es)
Resumo(s)
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.
Descrição
Palavras-chave
Aldosterone Gene transcription Glucocorticoid receptor Kidney Mineralocorticoid receptor Phosphorylation Steroid hormone receptor Cortisol . Faculdade de Ciências Exatas e da Engenharia
Contexto Educativo
Citação
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.
Editora
Elsevier