Fig. 1. Basic scheme for -arrestin negative feedback and GPCR endocytosis. Agonist exposure stimulates activation of GPCR, which leads to the dissociation of G proteins into activated subunit and dimers and triggers the activation of various effectors, such as adenylate cyclase and phospholipase C. The agonist-occupied GPCR is phosphorylated by GRKs, leading to signal desensitization, binding of -arrestin to the activated, phosphorylated GPCR and subsequent endocytosis of the receptor.