FK506-binding protein 12 modulates μ-opioid receptor phosphorylation and protein kinase C(ε)-dependent signaling by its direct interaction with the receptor.

ABSTRACT: Protein kinase C (PKC) activation plays an important role in morphine-induced μ-opioid receptor (OPRM1) desensitization and tolerance development. It was recently shown that receptor phosphorylation by G protein-coupled receptor kinase regulates agonist-dependent selective signaling and that inefficient phosphorylation of OPRM1 leads to PKCε activation and subsequent responses. Here, we demonstrate that such receptor phosphorylation and PKCε activation can be modulated by FK506-binding protein 12 (FKBP12). Using a yeast two-hybrid screen, FKBP12 was identified as specifically interacting with OPRM1 at the Pro(353) residue. In human embryonic kidney 293 cells expressing OPRM1, the association of FKBP12 with OPRM1 decreased the agonist-induced receptor phosphorylation at Ser(375). The morphi

SUBMITTER: Qiu Y 

PROVIDER: S-EPMC3868904 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature