| Project/Area Number |
18599006
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Yokohama City University |
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Principal Investigator |
SATO Motohiko Yokohama City University, Cardiovascular Research Institute, School of Medicine, Associate professor (40292122)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Satoshi Yokohama city University, Cardiovascular Research Institute, School of Medicine, Associate professor (60233475)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | G-protein / Signal trasnduction / Cardiovascular disease |
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| Research Abstract |
Recent data indicate the existence of signal regulators that directly influence the activation state of G-proteins independent of a GPCR. As part of a strategy to identify such entities involved in the development of cardiovascular disease, we utilized a functional screen in the yeast for the receptor-independent activators of heterotrimeric G-protein signaling and identified activators of G-protein signaling (AGS) 8 from rat heart following treatment of repetitive ischemia. We report here the extension of this approach to identify AGS involved in the development of cardiac hypertrophy. cDNA libraries were generated from hypertrophic heart of the mouse following treatment of isoproterenol (60 ug/g/day) or transverse aorta constriction for 7-9 days. The libraries were applied to the yeast system expressing Gsα or Giα3 as well as Gα16. Using the Giα3 yeast strain, we isolated cDNAs encoding AGS2 and 3 as well as RGS12. Using the Gα16 yeast strain, we isolated 3 candidates for novel AGS (novel-AGSs) representing 3 unique coding sequences belonged to the same functional group. The bioactivity of novel-AGSs was also observed in yeast strains expressing Gas, but not Gαi3. By interfacing to Gαl 6 or Gas signaling pathways, novel-AGSs may contribute to the development of cardiac hypertrophy.
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