Analysis of signal transduction in glycolipid microdomains
| Project/Area Number |
26440071
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
KASAHARA Kohji 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 副室長 (60250213)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 脂質ラフト / 糖脂質ミクロドメイン / シグナル伝達 / ラフト / 血小板 |
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| Outline of Final Research Achievements |
SDF-1α-induced platelet aggregation is mediated through its G protein-coupled receptor CXCR4 and PI3K. Here, we demonstrate that SDF-1α induces phosphorylation of Akt at Thr308 and Ser473 in platelets. SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by the CXCR4 antagonist AMD3100 or the PI3K inhibitor LY294002. SDF-1α-induced platelet aggregation is inhibited by pretreatment with the Akt inhibitor MK-2206 in a dose-dependent manner. Furthermore,SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the raft-disrupting agent methyl-β-cyclodextrin. Sucrose density gradient analysis shows that 35% of CXCR4, 93% of the heterotrimeric G proteins Gαi-1, 91% of Gαi-2, 50% of Gβ and 4.0% of PI3Kβ, and 4.5% of Akt2 are localized in the detergent-resistant membrane raft fraction. These findings suggest that SDF-1α/CXCR4 signaling in lipid rafts induces platelet aggregation via PI3K-dependent Akt phosphorylation.
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Report
(5 results)
Research Products
(18 results)
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[Journal Article] SDF-1α/CXCR4 signaling in lipid rafts induces platelet aggregation via PI3 kinase-dependent Akt phosphorylation.2017
Author(s)
Ohtsuka H, Iguchi T, Hayashi M, Kaneda M, Iida K, Shimonaka M, Hara T, Arai M, Koike Y, Yamamoto N, Kasahara K.
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Journal Title
PLoS One
Volume: 12
Issue: 1
Pages: e0169609-e0169609
DOI
Related Report
Peer Reviewed / Open Access
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