Fig. 7
From: Peroxiredoxin 6 mediates Gαi protein-coupled receptor inactivation by cJun kinase
Model of GPCR inactivation by PRDX6-mediated oxidation and depalmitoylation. a Proposed model of JNK-mediated Gαi regulation by norBNI- and morphine-like drugs. JNK promotes membrane localization of PRDX6 and PLA2 activity, thereby locally activating NADPH oxidase (NOX) and stimulating the generation of ROS. The Gαi-PRDX6 interaction may help promote PRDX6 translocation and/or locally target PLA2 activity. Gαi oxidation disrupts Gαi palmitoylation, jamming the G-protein receptor complex in an inactive conformation. b Oxidation of cys-3 of Gαi blocks repalmitoylation of the residue. c Proposed model of GPCR cross-regulation by this mechanism. ROS generated as result JNK/PRDX6 activation by GPCR (i.e., KOR) diffuse locally, oxidizing nearby GPCR-Gαi complexes, function as paracrine or intracrine signals to silence inhibitory GPCRs
