FIGURE 15-14 General mechanism of the activation of effector proteins associated with G protein–coupled receptors. Light colors denote the inactive and dark colors the active conformations of each protein. The G_α and G_βγ subunits of a heterotrimeric G protein are tethered to the membrane by covalently attached lipid molecules (wiggly black lines). Following ligand binding, exchange of GDP for GTP, and dissociation of the G protein subunits (steps 1 – 4), the free G_α·GTP binds to and activates an effector protein (step 5). Hydrolysis of GTP terminates signaling and leads to reassembly of the heterotrimeric G protein, returning the system to the resting state (step 6). Binding of another ligand molecule causes repetition of the cycle. In some pathways, the effector protein is activated by the free G_βγ subunit. See W. Oldham and H. Hamm, 2006, Quart. Rev. Biophys. 39:117.