2020 Fiscal Year Final Research Report
Analysis of substrate recognition and regulatory mechanisms for protein kinases.
Project/Area Number |
17K07383
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Cell biology
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Research Institution | Nagoya University |
Principal Investigator |
Amano Mutsuki 名古屋大学, 医学系研究科, 准教授 (90304170)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Keywords | リン酸化 / プロテインキナーゼ / 細胞内シグナル伝達 |
Outline of Final Research Achievements |
In this study, we analyzed substrate recognition and regulatory mechanisms of protein kinases, as well as physiological and pathological functions. We identified the specific sequences of MYPT1, a substrate for Rho-kinase, as docking motifs (DMs) conferring selectivity and efficiency of phosphorylation by Rho-kinase. We also found that longer intrinsically disordered regions (IDRs) are preferably phosphorylated by stochastic simulation model using our screening dataset for 15 protein kinases. In addition, functional analyses revealed that MAPK-Npas4/MKL2 (mouse striatal neurons) and PKN-MKL1 (mouse heart) signals are involved in dopamine-induced gene expression and stress-induced cardiac dysfunction, respectively.
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Free Research Field |
生化学・細胞生物学
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Academic Significance and Societal Importance of the Research Achievements |
タンパク質リン酸化は細胞内シグナル伝達に中心的な役割を果たし、生理機能のみならず種々の疾患に深く関わっている。本研究では、独自に開発したキナーゼ基質スクリーニング法(KISS法)より得られたデータを基に、リン酸化シグナルを理解するための分子基盤(キナーゼの基質認識機構)、および種々のキナーゼー基質シグナルの疾患への関わりについて理解を深めることができた。
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