Roles of G protein and beta-arrestin in dopamine D2 receptor-mediated ERK activation |
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Authors: | Quan Wenying Kim Ju-Heon Albert Paul R Choi Hyunjin Kim Kyeong-Man |
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Institution: | a Department of Pharmacology, College of Pharmacy, Chonnam National University, Kwang-Ju 500-757, Republic of Korea b Ottawa Health Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, Canada K1H-8M5 |
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Abstract: | 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. |
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Keywords: | Dopamine D2 receptor ERK β-Arrestin G protein |
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