Item type |
デフォルトアイテムタイプ_(フル)(1) |
公開日 |
2023-03-18 |
タイトル |
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タイトル |
Regulation of melanin-concentrating hormone receptor 1 signaling by RGS8 with the receptor third intracellular loop |
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言語 |
en |
作成者 |
Miyamoto-Matsubara, Mayumi
Saitoh, Osamu
Maruyama, Kei
Aizaki, Yoshimi
Saito, Yumiko
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アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
権利情報 |
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権利情報 |
Copyright (c) 2008 Elsevier Inc. |
主題 |
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主題Scheme |
Other |
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主題 |
MCH |
主題 |
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主題Scheme |
Other |
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主題 |
MCH receptor |
主題 |
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主題Scheme |
Other |
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主題 |
RGS protein |
主題 |
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主題Scheme |
Other |
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主題 |
Calcium |
主題 |
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主題Scheme |
Other |
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主題 |
Basic motif |
主題 |
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主題Scheme |
Other |
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主題 |
Signaling complex |
主題 |
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主題Scheme |
NDC |
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主題 |
460 |
内容記述 |
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内容記述 |
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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言語 |
en |
出版者 |
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出版者 |
Elsevier Science Inc. |
言語 |
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言語 |
eng |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
出版タイプ |
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出版タイプ |
AO |
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出版タイプResource |
http://purl.org/coar/version/c_b1a7d7d4d402bcce |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
10.1016/j.cellsig.2008.07.019 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
http://dx.doi.org/10.1016/j.cellsig.2008.07.019 |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
0898-6568 |
収録物識別子 |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA10671314 |
開始ページ |
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開始ページ |
2084 |
書誌情報 |
Cellular Signalling
Cellular Signalling
巻 20,
号 11,
p. 2084-2094,
発行日 2008-11
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旧ID |
25971 |