(American Association for the Advancement of Science (AAAS), 2021-03-12) Smith, Jeffrey; Pack, Thomas F.; Inoue, Asuka; Lee, Claudia; Zheng, Kevin; Choi, Issac; Eiger, Dylan S.; Warman, Anmol; Xiong, Xinyu; Ma, Zhiyuan; Viswanathan, Gayathri; Levitan, Ian M.; Rochelle, Lauren K.; Staus, Dean P.; Snyder, Joshua C.; Kahsai, Alem W.; Caron, Marc G.; Rajagopal, Sudarshan
G protein–coupled receptors (GPCRs) normally transmit signals by coupling to heterotrimeric guanine nucleotide–binding proteins (G proteins) or by binding β-arrestin proteins. Smith et al. provide evidence for another mechanism, an approximate combination of the two. They monitored the interaction of vasopressin type 2 receptors (V2Rs) and Gα proteins in cultured cells using bioluminescent resonance energy transfer. Even though V2Rs do not signal canonically through Gαi proteins, they promoted the formation of complexes containing β-arrestin and Gαi, and this led to downstream signaling to extracellular signal-regulated kinase protein kinases.
