GRK2 and GRK5 were essential for R399-induced GPBAR–β-arrestin 1 association. (A) Effects of GRK2, GRK5, or GRK6 on the R399-induced bioluminescence resonance energy transfer (BRET) assay. (B) Effects of knockdown of GRK2, GRK5, or GRK2 and GRK5 on R399-induced β-arrestin 1 recruitment. (C and D) Effects of GRK2 and GRK5 silencing on changes in TEAD-relative luciferase activity induced by R399 (700 nM) and on R399-induced cell growth were evaluated by MTT analysis (n = 6). All data are presented as the mean ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 based on the Student’s t-test. CTRL, control; DMSO, dimethyl sulfoxide; ns, not significant.