Regulation of melanin-concentrating hormone receptor 1 signaling by RGS8 with the receptor third intracellular loop
Cellular Signalling 20 巻 11 号
2084-2094 頁
2008-11 発行
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CellSignal_20_2084.pdf
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種類 :
全文
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タイトル ( eng ) |
Regulation of melanin-concentrating hormone receptor 1 signaling by RGS8 with the receptor third intracellular loop
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作成者 |
Miyamoto-Matsubara Mayumi
Saitoh Osamu
Maruyama Kei
Aizaki Yoshimi
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収録物名 |
Cellular Signalling
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巻 | 20 |
号 | 11 |
開始ページ | 2084 |
終了ページ | 2094 |
抄録 |
Melanin-concentrating hormone (MCH) receptor 1 (MCH1R) belongs to the class A G protein-coupled receptors (GPCRs). The MCH-MCH1R system plays a central role in energy metabolism, and thus the regulation of signaling pathways activated by this receptor is of particular interest. Regulator of G protein signaling (RGS) proteins work by increasing the GTPase activity of G protein α subunits and attenuate cellular responses coupled with G proteins. Recent evidence has shown that RGS proteins are not simple G protein regulators but equally inhibit the signaling from various GPCRs. Here, we demonstrate that RGS8, which is highly expressed in the brain, functions as a negative modulator of MCH1R signaling. By using biochemical approaches, RGS8 was found to selectively and directly bind to the third intracellular (i3) loop of MCH1R in vitro. When expressed in HEK293T cells, RGS8 and MCH1R colocalized to the plasma membrane and RGS8 potently inhibited the calcium mobilization induced by MCH. The N-terminal 9 amino acids of RGS8 were required for the optimal capacity to downregulate the receptor signaling. Furthermore, Arg253 and Arg256 at the distal end of the i3 loop were found to comprise a structurally important site for the functional interaction with RGS8, since coexpression of RGS8 with R253Q/R256Q mutant receptors resulted a loss of induction of MCH-stimulated calcium mobilization. This functional association suggests that RGS8 may represent a new therapeutic target for the development of novel pharmaceutical agents.
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著者キーワード |
MCH
MCH receptor
RGS protein
Calcium
Basic motif
Signaling complex
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NDC分類 |
生物科学・一般生物学 [ 460 ]
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言語 |
英語
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資源タイプ | 学術雑誌論文 |
出版者 |
Elsevier Science Inc.
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発行日 | 2008-11 |
権利情報 |
Copyright (c) 2008 Elsevier Inc.
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出版タイプ | Author’s Original(十分な品質であるとして、著者から正式な査読に提出される版) |
アクセス権 | オープンアクセス |
収録物識別子 |
[ISSN] 0898-6568
[DOI] 10.1016/j.cellsig.2008.07.019
[NCID] AA10671314
[DOI] http://dx.doi.org/10.1016/j.cellsig.2008.07.019
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