Development of optical technology for quantitative regulation of intracellular kinases

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22241
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Tohoku University
• Principal Investigator: Mizukami Shin 東北大学, 多元物質科学研究所, 教授 (30420433)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: タンパク質ラベル化技術 / リン酸化酵素 / 光薬理学

Outline of Final Research Achievements

Optical modulation of specific enzyme activity in a living cell can lead to elucidating unknown physiological functions of the target enzyme. We tried to develop techniques for photo-regulation of specific intracellular enzyme activities using our developed photoreversible protein labeling technology. First, epidermal growth factor receptor (EGFR) was selected as the target molecule, due to the difficulty in synthesizing the designed photoresponsive molecule, the target was changed to a mitophagy-related kinase, PINK-1. We succeeded in developing a photoregulation system of the subcellular targeting of PINK-1 and in optically inducing mitophagy through the phosphorylation by PINK-1.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

細胞内の酵素活性を光制御する技術は、基礎生物学から医学・薬学に至るまで幅広い領域の研究で活用できる重要な基盤技術となり得る。本研究で得られた成果は、開発した手法が単に特定の酵素の機能を制御する手法を提供するだけでなく、他の酵素・タンパク質にも応用可能な普遍的な技術であることを示している。今後、標的蛋白質（PINK-1）の未知の機能の解明や、より詳細な細胞内シグナル伝達機構の解明に繋がることが期待される。