Extracellular diacyl phospholipids
| Project/Area Number |
19K22508
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 48:Biomedical structure and function and related fields
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Sasaki Takehiko 東京医科歯科大学, 難治疾患研究所, 教授 (50333365)
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| Project Period (FY) |
2019-06-28 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | リン脂質 / リン脂質シグナリング / 生理活性脂質 |
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| Outline of Research at the Start |
申請者は最近、独自に開発したPIP3測定法によって、これまで細胞形質膜の内層に限局すると考えられていたPIP3が、血液中や細胞培養上清など細胞外にも存在することを発見した。多くのがん細胞では、PIP3の生成亢進や分解抑制が起きており、細胞膜に蓄積したPIP3は細胞内シグナル伝達因子として機能している。そのような細胞から分泌されたPIP3の細胞外機能について解明したい。
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| Outline of Final Research Achievements |
Structure-activity relationship of macrophage activation by extracellular PIP3 was clarified using cytokine production as an indicator. The findings suggested the existence of specific receptors.
We found that extracellular PIP3 induced cytoskeletal reorganization in various cancer cell lines. About 50 cultured cell lines were examined, but only some of them were sensitive. Gene expression in 30 breast cancer cell lines was analyzed by RNA seq, and membrane proteins that correlated with PIP3 sensitivity were narrowed down to candidate receptor proteins.
We conducted receptor screening based on the working hypothesis that the PIP3 receptor belongs to the GTP-binding protein-coupled receptor family.
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| Academic Significance and Societal Importance of the Research Achievements |
PIP3が新しいホルモン/オータコイドであれば、現在の膜構成因子としてのドグマでは目が向けられていない、PIP3の新規の生理活性とその発現機構が明らかになるなど、これまで見逃されていた生体調節機構の発見につながる可能性があることから、本研究は細胞膜脂質研究をはじめ生命科学の様々な研究分野の体系や考え方の方向を大きく転換する潜在性を有すると考えている。
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Report
(2 results)
Research Products
(11 results)
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[Journal Article] A Peptide Derived from Phosphoinositide 3-kinase Inhibits Endocytosis and Influenza Virus Infection2019
Author(s)
Fujioka Y, Satoh AO, Horiuchi K, Fujioka M, Tsutsumi K, Sasaki J, Nepal P, Kashiwagi S, Paudel S, Nishide S, Nanbo A, Sasaki T, Ohba Y
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Journal Title
Cell Structure and Function
Volume: 44
Issue: 1
Pages: 61-74
DOI
NAID
ISSN
0386-7196, 1347-3700
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A Negative Feedback Loop Regulates Integrin Inactivation and Promotes Neutrophil Recruitment to Inflammatory Sites2019
Author(s)
McCormick Barry, Craig Helen E., Chu Julia Y., Carlin Leo M., Canel Marta, Wollweber Florian, Toivakka Matilda, Michael Melina, Astier Anne L., Norton Laura, Lilja Johanna, Felton Jennifer M., Sasaki Takehiko, Ivaska Johanna, Hers Ingeborg, Dransfield Ian, Rossi Adriano G., Vermeren Sonja
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Journal Title
JOURNAL OF IMMUNOLOGY
Volume: 203
Issue: 6
Pages: 1579-1588
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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