Comprehensive profiling of substrate recognition motifs for human kinome

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02466
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43060:System genome science-related
• Research Institution: Kyoto University
• Principal Investigator: Sugiyama Naoyuki 京都大学, 薬学研究科, 准教授 (50545704)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: プロテオミクス / シグナル伝達 / タンパク質キナーゼ / 質量分析

Outline of Final Research Achievements

To elucidate the functions and roles of human kinome in cells, comprehensive search of kinase substrate motifs and kinase-binding motifs in all human proteome and the kinase responsible for protein phosphorylation reactions occurring in vivo was predicted and identified at the kinome level. Based on the identified motifs, we designed artificial substrate peptides that are hyper-selectively phosphorylated by each kinase,and experimentally evaluated their selectivity and sensitivity. Using the designed peptide libraries, we developed a method to measure intracellular kinome activity. Furthermore, we have created substrate peptides in which the substrate sequence is linked to a kinase-binding motif.

Free Research Field

プロテオミクス

Academic Significance and Societal Importance of the Research Achievements

各キナーゼの生理的条件下における基質選択性の予測、およびキナーゼ高選択的選択的基質ペプチドによるキナーゼ活性の一斉計測が可能になったことにより、大規模リン酸化プロテオームデータの有効活用と補間、シグナル伝達の詳細な制御機構や細胞内リン酸化ネットワークの全体像の解明につながることが期待できる。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も応用可能であると考える。