FIGURE 8.

Schematic model of AT1R signaling induced by different modes of receptor activation. Different stimulations stabilize the receptors into distinct active conformational states, allowing the recruitment of unique subsets of transducers that subsequently activates divergent arrays of downstream signaling. When induced by the balanced agonist AngII, the AT1Rs transduce signaling through both Gα_q and β-arrestins, whereas the biased agonists TRV120023 and TRV120026 preferentially induce β-arrestin signaling without activating G proteins. In contrast, another β-arrestin-biased receptor stimulation, mechanical stress, specifically promotes the recruitment of Gα_i to the receptors and activates β-arrestin signaling through a mechanism distinct from that induced by the biased ligands