| Project/Area Number |
14370737
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
NAKAHATA Norimichi TOHOKU UNIVERSITY, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, PROFESSOR, 大学院・薬学研究科, 教授 (60045804)
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| Co-Investigator(Kenkyū-buntansha) |
HONMA Shigeyoshi TOHOKU UNIVERSITY, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, RESEARCH ASSOCIATE, 大学院・薬学研究科, 教務職員 (20344682)
OHKUBO Satoko TOHOKU UNIVERSITY, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, INSUTORUCTOR, 大学院・薬学研究科, 助手 (20274954)
YOSHIDA Makoto TOHOKU UNIVERSITY, GRADUATE SCHOOL OF PAHRMACEUTICAL SCIENCES, ASSOCIATE PROFFESOR, 大学院・薬学研究科, 助教授 (90201011)
SUKEGAWA Jun TOHOKU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学系研究科, 助教授 (30187687)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2003: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2002: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Keywords | G protein-coupled receptor / thromboxane A_2 receptor / PTH receptor / proteasme / G_<12> / Tctes-1 / 4.1G / two hybrid system / two hybrid システム / TP-α / TP-β / PA28γ / α7 |
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| Research Abstract |
Since the ligands to G protein coupled receptors (GPCRs) are utilized for the, treatment of many diseases, it is important to investigate the signal transduction in GPCRs for developing the new effective drugs. Recently, it has been clarified that stimulation of one GPCR results in the multiple responses, although the molecular mechanism has not been clarified. In the present study, we tried to clarify the mechanism in GPCR-mediated multiple signal transduction.
To examine the protein directly bound to thromboxane A_2 receptor (TP), yeast two hybrid system was employed. It was found that carboxyl terminal of TP-β, but not TP-α, proteasome activator PA28γ and proteasome subunit α7. Furthermore, an inhibitor of proteasome accelerated, the expression of TP-β, but not TP-α. On the other hand, it has been examined whether TP communicates with G_<12> family G protein using the adenovirus coding the Gα_2 or Gα_<13>. We found that TP clearly communicate G_<12> and G_<13> in addition of Gq. Moreover, we found that C terminal of PTH receptor communicates with Tctex-1 and 4.1G, which show a role of internalization PTH receptor or expression of the receptor in plasma membranes, respectively. Thus, we clarify, the several important regulatory mechanism of GPCR-mediated signal transduction in the present study.
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