Manifold roles of β-arrestins in GPCR signaling elucidated with siRNA and CRISPR/Cas9

Authors: Louis M. Luttrell, Jialu Wang, Bianca Plouffe, Jeffrey S. Smith, Lama Yamani, Suneet Kaur, Pierre‐Yves Jean‐Charles, Christophe Gauthier, Mi‐Hye Lee, Biswaranjan Pani, Ji‐Hee Kim, Seungkirl Ahn, Sudarshan Rajagopal, Éric Reiter, Michel Bouvier, Sudha K. Shenoy, Stéphane A. Laporte, Howard A. Rockman, Robert J. Lefkowitz - Science Signaling 2018 cited by 213

AR-mediated stimulation of ERK1/2 to become more dependent on G proteins, which was reversed by reintroducing βArr1/2. These data suggest that βArr1/2 function as a regulatory hub, determining the balance between mechanistically different pathways that result in activation of ERK1/2, and caution against extrapolating results obtained from βArr1/2- or G protein-deleted cells to GPCR behavior in native systems.