2019 Fiscal Year Final Research Report
Identification of endogenous kinase substrates for analyzing intracellular signaling pathway
| Project/Area Number |
17H03605
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | キナーゼ / キナーゼ基質 / リン酸化プロテオーム / 細胞内シグナル伝達 |
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| Outline of Final Research Achievements |
The goal of this study is to establish a method to identify the endogenous kinase substrates on a large scale, and to apply to intracellular signal pathway analysis. To accomplish this goal, we have developed three methods as follows: (1) a method to measure changes in phosphorylation upon kinase perturbation, (2) a method to calculate the motif score based on the extracted phosphorylation motif of each kinase from in vitro kinase assay, and (3) a method to analyze the kinase-substrate transient interactions. These three methods were combined and applied to identifying endogenous kinase substrates successfully. In addition, we developed a method for estimating the activated kinase from the phosphoproteome information based on kinase-substrate relationships.
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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 |
国内外のゲノムワイド関連解析により、様々な疾病原因は個々の遺伝子よりもシグナルパスウェイ毎の異常に集積されており、特に癌は十数種のパスウェイに原因遺伝子が分布することがわかってきた。これらのパスウェイにはすべてリン酸化シグナルが関わっており、その異常はガンそのものの発症因子ともなり、その進行、薬剤感受性および治療予後とも深く関わる。本研究の成果により、様々なパスウェイ毎のリン酸化動態を全体として理解することが可能となり、がんをはじめとする疾病の分子基盤の解明につながるものと期待される。
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