Fig. 1.
Examples of G protein- and β-arrestin-mediated downstream signaling pathways on GPCRs. Upon agonist binding to GPCRs, both G proteins (Gα12, Gαq/11, Gαi/o, Gαs, Gβ and Gγ subunits) and β-arrestin are activated to mediate a variety of distinct downstream signaling pathways. Stimulation of Gβ subunit can activate PI3Kγ and Gγ subunit can activate PKD. Gα12 can activate Rho kinase signaling pathways and Gαq can induce the mobilization of calcium from intracellular stores through activation of PLC/IP3. Gαo signaling activates MEK/ERK pathway to mediate cell cycle progression. Gαs proteins promote AC-induced PKA activation. Phosphorylation of GPCRs by GRK results in the recruitment of β-arrestin, which in turn desensitizes G protein signaling, mediates receptor trafficking to endosomes, and activates β-arrestin-dependent signaling.