Fig. 2.

Schematic diagram of GPCRs signaling steps, A)- G protein-dependent signaling; Following binding of agonist to the extracellular domain of receptor results in conformation change of receptor including cytosolic c-Terminus leading to recruit specific heterotrimeric G protein. Exchange of GDP by GTP of Gα subunit (Gαq, Gαs, Gαi, and Gα12/13) results in dissociation of heterotrimeric G proteins and downstream signaling of Gα from βγ. B)- G protein independent signaling; Following termination of first wave signals by PKC, PKA, or GRKs that lead to β-Arrestins recruitment to c-terminus of the receptor. β-Arrestins will prevent further G proteins coupling, facilitate internalization of receptor and act as a scaffold for MAP kinase signaling as a second signal wave.