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KMID : 0043320080310040474
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Archives of Pharmacal Research
2008 Volume.31 No. 4 p.474 ~ p.481
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Characterization of Functional Roles of DRY Motif in the Intracellular Loop of Dopamine and Receptors
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Kim Ju-Heon
Cho Eun-Young
Min Cheng-Chun
Park Jae-H
Kim Kyeong-Man
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Abstract
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Dopamine and show very high sequence homology and employ virtually identical signaling pathways even though is times more active. Among the structural motifs identified, a triplet sequence, Asp-Arg-Tyr (DRY motif), plays critical roles in the determination of receptor conformations for signaling and intracellular trafficking of G protein-coupled receptors by forming intramolecular interactions. Thus, it is possible that different signaling efficiencies of and might be caused by the receptor activation levels stabilized by their own DRY motifs. In this study, the Arg and Asp residues of and were mutated, and resulting changes in their signaling and intracellular trafficking properties were comparatively studied. Mutation of the Arg residues of and abolished their signaling but differently affected their intracellular localizations. The wildtype and were expressed mainly on the plasma membrane. On the other hand, compared with the wildtype , a substantial amount of was localized intracellularly. The expression of receptor proteins on the plasma membrane and their signaling efficiencies were more drastically affected by the mutation of the Asp residue of than . Therefore, it was concluded that the different levels of conformational strain exerted by the DRY motif might partly determine the quantitative differences in the signaling efficiencies between and .
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KEYWORD
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Dopamine, and , receptor, Dry motif, Signaling, Desensitization, G protein
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