The Role of Sequestration in G Protein-coupled Receptor Resensitization

摘要: G protein-coupled receptor kinases phosphorylate the agonist occupied conformation of receptors in plasma membrane, leading to their desensitization. Receptor resensitization requires dephosphorylation, a process which is mediated by and vesicular membrane-associated form PP-2A. We present evidence that, like phosphorylation, dephosphorylation tightly regulated, requiring specific induced acidification. In vitro, spontaneous phosphorylated observed only at acidic pH. Furthermore, intact cells upon stimulation, traffic from membrane vesicles where they become physically associated with phosphatase dephosphorylated. Treatment NH4Cl, disrupts pH found endosomal vesicles, blocks association dephosphorylation. These findings suggest that conformational change acidification key determinant regulating resensitization.