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

Jiménez-Canino, Rubén; Fernandes, Miguel X.; Alvarez de la Rosa, Diego

http://hdl.handle.net/10400.13/5029

Use this identifier to reference this record.

Name:	Description:	Size:	Format:
Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors.pdf		2.27 MB	Adobe PDF	Download

Send Feedback

Authors

Jiménez-Canino, Rubén

Fernandes, Miguel X.

Alvarez de la Rosa, Diego

Abstract(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.

Keywords

Aldosterone Gene transcription Glucocorticoid receptor Kidney Mineralocorticoid receptor Phosphorylation Steroid hormone receptor Cortisol . Faculdade de Ciências Exatas e da Engenharia

URI

http://hdl.handle.net/10400.13/5029

Citation

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.