Establishment of substrates for receptor tyrosine phosphatase and its application

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07348
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Nagoya University
• Principal Investigator: SAKAMOTO Kazuma 名古屋大学, 医学系研究科, 准教授 (60612801)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 受容体型チロシンホスファターゼ / 軸索再生 / 近位依存性標識 / 基質 / タンパク質相互作用

Outline of Final Research Achievements

In this study, I aimed to establish a method for the comprehensive identification of substrates of receptor-type tyrosine phosphatases (RPTPs). In particular, we focused on PTPσ, a member of the RPTP family that is involved in the inhibition of axon regeneration in the central nervous systems. I applied a proximity-dependent ligation assay to identify the interacting molecules for PTPσ. As a result, approximately 100 proteins were identified as PTPσ interactors. This list included already-known interactors such as Liprin-α and Trio. Among these molecules, those involved in axon elongation were validated for their tyrosine phosphorylation and dephosphorylation by PTPσ. Together, a proximity-dependent ligation assay seems to be a powerful tool for the comprehensive identification of substrates for RPTP.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

近位依存性標識法を用いることにより、これまでに困難であったRPTPの基質同定を簡便に行うことができることを示した。既知分子も再現性よくフォローされており、本手法は信頼性も十分に担保されている。これまでにRPTPは神経疾患やがん、炎症性疾患や代謝性疾患に関与していることが報告されている。ヒト疾患において標的とするには、基質分子の不明瞭さが律速段階になっていたが、本手法の利用により、RPTPのバイオロジーの理解につながることが期待できる。