TY  - JOUR
AU  - Jiménez-Canino, R.
AU  - Fernandes, M.X.
AU  - De La Rosa, D.A.
T1  - Phosphorylation of mineralocorticoid receptor ligand binding domain impairs receptor activation and has a dominant negative effect over non-phosphorylated receptors
LA  - eng
PY  - 2016
SP  - 19068
EP  - 19078
T2  - Journal of Biological Chemistry
SN  - 1083-351X
VL  - 291
IS  - 36
PB  - American Society for Biochemistry and Molecular Biology Inc.
PP  - Bethesda
AB  - 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.
DO  - 10.1074/JBC.M116.718395
UR  - https://portalciencia.ull.es/documentos/5e39b7622999523aa92712b7
DP  - Dialnet - Portal de la Investigación
ER  -