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. Author manuscript; available in PMC: 2013 Apr 17.
Published in final edited form as: Annu Rev Pharmacol Toxicol. 2011 Sep 19;52:179–197. doi: 10.1146/annurev.pharmtox.010909.105800

Figure 4.

Figure 4

G protein–coupled receptor kinase (GRK)-mediated phosphorylation “bar code” at the C terminus of seven-transmembrane receptors (7TMRs) converts ligand-induced conformation of the receptor into selective β-arrestin intracellular functions. A general model for β-arrestin-biased ligand mechanism of action is proposed (78, 80, 82). GRK2/3 and GRK5/6 exert qualitatively different actions. GRK2/3 require Gβ for membrane recruitment and activation and phosphorylate specific serines and threonines in the receptor’s C-tail; the GRK2/3-mediated phosphorylation “bar code” then leads to desensitization and internalization upon β-arrestin recruitment. GRK5/6 do not require G proteins for their activation; the GRK5/6-dependent phosphorylation “bar code” then creates a signaling platform in which β-arrestin bridges the activated receptor to partners involved in intracellular signaling such as the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase (ERK) module. Other abbreviation: MEK, MAP kinase/extracellular signal-regulated kinase kinase.