Roles of G protein and β-arrestin in dopamine D2 receptor-mediated ERK activation

ERK activation by dopamine D2 receptor (D2R) has been extensively characterized in various cell types including brain tissues. However, the involvement of β-arrestin in the D2R-mediated ERK activation is not clear yet. Three different strategies were employed in this study to determine the roles of G protein or β-arrestin in D2R-mediated ERK activation. The cellular level of β-arrestins was reduced by RNA interference and pertussis toxin-insensitive Gi proteins were used to identify the G protein involved. Finally point mutations of D2R in which coupling with G protein was abolished but the interaction with β-arrestin was increased, were employed to determine whether the affinity between D2R and β-arrestin is a critical factor for β-arrestin-mediated ERK activation. Our results show that Gi2 protein is involved in D2R-mediated ERK activation but β-arrestins are either not involved or play minor role.