| Item type |
文献 / Documents(1) |
| 公開日 |
2022-01-04 |
| アクセス権 |
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アクセス権 |
open access |
| 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 |
| 出版社版DOI |
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|
識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1074/jbc.ra120.013988 |
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言語 |
ja |
|
|
関連名称 |
10.1074/jbc.ra120.013988 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
15-Keto-PGE2 acts as a biased/partial agonist to terminate PGE2-evoked signaling |
|
言語 |
en |
| タイトル別表記 |
|
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その他のタイトル |
15-keto-PGE2 acts as switched agonist of EP receptors |
|
言語 |
en |
| 著者 |
エンドウ, スズ
スガナミ, アキコ
福島, 圭穣
セノオ, カナホ
アラキ, ユミ
Regan, John W.
マシモ, マサト
タムラ, ユタカ
藤野, 裕道
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| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Prostaglandin E2 (PGE2) is well-known as an endogenous proinflammatory prostanoid synthesized from arachidonic acid by the activation of cyclooxygenase-2. E type prostanoid (EP) receptors are cognates for PGE2 that have four main subtypes: EP1 to EP4. Of these, the EP2 and EP4 prostanoid receptors have been shown to couple to Gαs-protein and can activate adenylyl cyclase to form cAMP. Studies suggest that EP4 receptors are involved in colorectal homeostasis and cancer development, but further work is needed to identify the roles of EP2 receptors in these functions. After sufficient inflammation has been evoked by PGE2, it is metabolized to 15-keto-PGE2. Thus, 15-keto-PGE2 has long been considered an inactive metabolite of PGE2. However, it may have an additional role as a biased and/or partial agonist capable of taking over the actions of PGE2 to gradually terminate reactions. Here, using cell-based experiments and in silico simulations, we show that PGE2-activated EP4 receptor–mediated signaling may evoke the primary initiating reaction of the cells, which would take over the 15-keto-PGE2–activated EP2 receptor–mediated signaling after PGE2 is metabolized to 15-keto-PGE2. The present results shed light on new aspects of 15-keto-PGE2, which may have important roles in passing on activities to EP2 receptors from PGE2-stimulated EP4 receptors as a “switched agonist.” This novel mechanism may be significant for gradually terminating PGE2-evoked inflammation and/or maintaining homeostasis of colorectal tissues/cells functions. |
|
言語 |
en |
| 書誌情報 |
en : Journal of Biological Chemistry
巻 295,
号 38,
p. 13338-13352,
発行日 2020-07-29
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
00219258 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA1202441X |
| 出版者 |
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出版者 |
American Society for Biochemistry and Molecular Biology |
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言語 |
en |
| 出版者 |
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出版者 |
Elsevier |
|
言語 |
en |
| 権利情報 |
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|
言語 |
en |
|
権利情報 |
This is an Open Access article under the CC BY license. |
| EID |
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|
識別子 |
379559 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
jbc_295_38_13338.pdf (1.94 MB)
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