Regulatory mechanisms of signaling pathways through GnRH receptor heterodimerization with a species-specific orphan receptor subtype
| Project/Area Number |
20770111
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional biochemistry
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| Research Institution | Suntory Institute for Bioorganic Research |
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Principal Investigator |
SAKAI Tsubasa Suntory Institute for Bioorganic Research, 研究員 (40414122)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | PCRヘテロダイマー / GnRH / 機能進化 / GPCR / ヘテロダイマー / ホヤ / ペプチド / へテロダイマー |
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| Research Abstract |
Four GnRH receptors (Ci-GnRHR1-4) were identified in the protochordate, Ciona intestinalis. A Ciona-specific GnRHR paralog, Ci-GnRHR4 (R4) has been regarded as an orphan or non-functional receptor. The dimerization between R1 and R4 in the ovary and in the transfected HEK293MSR cells was detected. The heterodimerization of R1 with R4 led to potentiation of Ca^<2+>-dependent activation of PKC< by tGnRH-6 and Ca^<2+>-independent activation of PKC by tGnRH-5 and 6, eventually leading to up-regulation of ERK phosphorylation in the MAPK cascade. These results provide evidence that R4 serves as an endogenous modulatory factor for the fine-tuning of signal transduction via heterodimerization with R1, and that GPCR heterodimerization with an orphan receptor is involved in the evolution of a unique pattern of signaling cascade regulation widely conserved in organisms.
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Report
(3 results)
Research Products
(14 results)
