| First Author | Jiménez-Canino R | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 36 | Pages | 19068-78 |
| PubMed ID | 27422824 | Mgi Jnum | J:236931 |
| Mgi Id | MGI:5810234 | Doi | 10.1074/jbc.M116.718395 |
| Citation | Jimenez-Canino R, et al. (2016) Phosphorylation of Mineralocorticoid Receptor Ligand Binding Domain Impairs Receptor Activation and Has a Dominant Negative Effect over Non-phosphorylated Receptors. J Biol Chem 291(36):19068-78 |
| abstractText | 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 mineralocorticoid receptor (MR) on Ser-843, a residue placed on the ligand binding domain, lowers affinity for agonists, producing inhibition 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 inhibitory effect of phosphorylation on MR acts in a dominant-negative manner, effectively amplifying its functional effect on gene transactivation. |
