2018 Fiscal Year Final Research Report
Phosphorylation netowork analysis based on in vitro kinase-substrate relationships
| Project/Area Number |
16K07198
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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 |
Genome biology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Research Collaborator |
NIINAE Tomoya
YOSHIKAWA Yuki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | プロテオミクス / シグナル伝達 / タンパク質キナーゼ |
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| Outline of Final Research Achievements |
To analyze a comprehensive overview of intracellular phosphorylation networks, we constructed phosphorylation model of individual human protein kinase based on in vitro kinase-substrate relationships, and developed a method for prediction of physiological kinase substrates.
The predicted kinase-substrate relationships were evaluated by using a large-scale quantitative phosphoproteome profiling, in which cultured cells were treated with or without a kinase inhibitor. Responsible kinases for the downregulated phosphorylation sites were predicted using the our method. As a result, we successfully predicted inhibition of targeted and its downstream kinases and found that the prediction accuracy is higher than that of the existing techniques.
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| Free Research Field |
プロテオミクス
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| Academic Significance and Societal Importance of the Research Achievements |
タンパク質のリン酸化は細胞内のシグナル伝達に非常に重要な役割を果たしており、リン酸化酵素であるキナーゼの異常は様々な疾患と関連があることが知られている。本研究では、細胞内情報伝達ネットワークの全体像の解明を目的として、細胞内に存在するキナーゼ群の基質となるタンパク質を予測する方法を開発した。
本研究によって開発した方法を用いて各キナーゼの詳細な機能や細胞内リン酸化ネットワークの全体像が明らかとなれば、タンパク質のリン酸化異常が関与する多くの疾病のメカニズム解明や病気の診断や層別化、新規な分子標的薬の開発につながることが期待できる。
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