Screening for peptide ligands that activate beta-arrestin biasd cell signaling of orphan GPCRs
Project/Area Number |
26460333
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General pharmacology
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Research Institution | The University of Tokyo |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
YANAGISAWA Masashi 国際統合睡眠医科学研究機構, 教授 (20202369)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | GPCR / Gタンパク質 / β-アレスチン / 生理活性ペプチド |
Outline of Final Research Achievements |
Our purpose of this study is to identify endogenouse ligands for orphan GPCRs by newly developed screening systems. We utilized two intracellular signaling pathways, G-proteins and β-arrestin for detection of GPCR activation. To detect β-arrestin signaling, we monitored the ligand activated GPCR-mediated β-arrestin recruitment by using enzymatic complementation of E. coli β-galactosidase, alpha and omega fragments. In terms of detection of G-protein signaling, we generated a new technology that simply monitoring activities of any G-protein alpha subunits leading to minimization of experimental steps. We have optimized these assay systems suitable for high through put screening and being conducting the screening.
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] A Periodontal pathogen Porphyromonas gingivalis deteriorates Isoproterenol-Induced myocardial remodeling in mice2017
Author(s)
Sato H, Suzuki JI, Aoyama N, Watanabe R, Kaneko M, Shiheido Y, Yoshida A, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, Komuro I, Isobe M, Izumi Y
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Journal Title
Hypertens Res.
Volume: 40
Issue: 1
Pages: 35-40
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Periodontitis and myocardial hypertrophy2017
Author(s)
Suzuki J, Sato H, Kaneko M, Yoshida A, Aoyama N, Akimoto S, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, IzumiY, Isobe M, Komuro I
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Journal Title
Hypertens Res
Volume: [Epub ahead of print]
Issue: 4
Pages: 324-328
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] A peptide vaccine targeting angiotensin II attenuates the cardiac dysfunction induced by myocardial infarction.2017
Author(s)
Watanabe R, Suzuki JI, Wakayama K, Maejima Y, Shimamura M, Koriyama H, Nakagami H, Kumagai H, Ikeda Y, Akazawa H, Morishita R, Komuro I, Isobe M.
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Journal Title
Sci Rep.
Volume: 7
Issue: 1
Pages: 43920-43920
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure.2017
Author(s)
Kamo T, Akazawa H, Suda W, Saga-Kamo A, Shimizu Y, Yagi H, Liu Q, Nomura S, Naito AT, Takeda N, Harada M, Toko H, Kumagai H, Ikeda Y, Takimoto E, Suzuki JI, Honda K, Morita H, Hattori M, Komuro I.
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Journal Title
PLoS One.
Volume: 12
Issue: 3
Pages: 0174099-0174099
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Toll-like receptor 4 signaling has a critical role in Porphyromonas gingivalis-accelerated neointimal formation after arterial injury in mice.2016
Author(s)
Kobayashi N, Suzuki JI, Aoyama N, Sato H, Akimoto S, Wakayama K, Kumagai H, Ikeda Y, Akazawa H, Komuro I, Izumi Y, Isobe M.
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Journal Title
Hypertens Res
Volume: 39
Issue: 10
Pages: 717-722
DOI
Related Report
Peer Reviewed
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[Journal Article] Periodontitis May Deteriorate Sinus of Valsalva Dilatation in Marfan Syndrome Patients2016
Author(s)
Suzuki J, Imai Y, Aoki M, Fujita D, Takeda N, Aoyama N, Wakayama K, Ikeda Y, Kumagai H, Akazawa H, Izumi Y, Isobe M, Komuro I, Hirata Y
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Journal Title
International Heart Journal
Volume: 57
Issue: 4
Pages: 456-460
DOI
NAID
ISSN
1349-2365, 1349-3299
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Quantitative measurement of GPCR endocytosis via pulse-chase covalent labeling2015
Author(s)
Kumagai H, Ikeda Y, Motozawa Y, Fujishiro M, Okamura T, Fujio K, Okazaki H, Nomura S, Takeda N, Harada M, Toko H, Takimoto E, Akazawa H, Morita H, Suzuki J, Yamazaki T, Yamamoto K, Komuro I, Yanagisawa M
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Journal Title
PLoS One
Volume: 10
Issue: 5
Pages: e0129394-e0129394
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Monitoring beta-arrestin recruitment via beta-lactamase enzyme fragment complementation: purification of peptide E as a low-affinity ligand for mammalian bombesin receptors2015
Author(s)
Ikeda Y*, Kumagai H*, Okazaki H, Fujishiro M, Motozawa Y, Nomura S, Takeda N, Toko H, Takimoto E, Akazawa H, Morita H, Suzuki J, Yamazaki T, Komuro I, Yanagisawa M (co-first author)
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Journal Title
PLoS One
Volume: 10
Issue: 6
Pages: e0127445-e0127445
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Acute Myocardial Infarction That Resulted From Poor Adherence to Medical Treatment for Giant Coronary Aneurysm2015
Author(s)
Motozawa Y, Uozumi H, Maemura S, Nakata R, Yamamoto K, Takizawa M, Kumagai H, Ikeda Y, Komuro I, Ikenouchi H
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Journal Title
International Heart Journal
Volume: 56
Issue: 5
Pages: 551-554
DOI
NAID
ISSN
1349-2365, 1349-3299
Related Report
Peer Reviewed / Open Access
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[Journal Article] A food-derived flavonoid luteolin protects against angiotensin II-induced cardiac remodeling2015
Author(s)
Nakayama A, Morita H, Nakao T, Yamaguchi T, Sumida T, Ikeda Y, Kumagai H, Motozawa Y, Takahashi T, Imaizumi A, Hashimoto T, Nagai R, Komuro I
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Journal Title
PLoS One
Volume: 10
Issue: 9
Pages: e0137106-e0137106
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Design and Synthesis of Non-Peptide, Selective Orexin Receptor 2 Agonists2015
Author(s)
Nagahara T, Saitoh T, Kutsumura N, Irukayama-Tomobe Y, Ogawa Y, Kuroda D, Gouda H, Kumagai H, Fujii H, Yanagisawa M, Nagase H
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Journal Title
J. Med. Chem
Volume: 58
Issue: 20
Pages: 7931-7937
DOI
Related Report
Peer Reviewed
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[Journal Article] Next Generation ARBs2015
Author(s)
Ikeda Y, Kumagai H, Motozawa Y, Suzuki J, Komuro I
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Journal Title
International Heart Journal
Volume: 56
Issue: 6
Pages: 585-586
DOI
NAID
ISSN
1349-2365, 1349-3299
Related Report
Peer Reviewed / Open Access