2023 Fiscal Year Final Research Report
The mechanisms of functional regulation of ErbB4 by N-glycans.
| Project/Area Number |
21K06083
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 43030:Functional biochemistry-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
藤谷 直樹 札幌医科大学, 医学部, 講師 (10374191)
上原 康昭 札幌医科大学, 医学部, 助教 (40882907)
長谷川 喜弘 札幌医科大学, 医学部, 講師 (90643180)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 糖鎖 / ErbB4 / ErbB / 増殖因子受容体 / シグナル伝達 |
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| Outline of Final Research Achievements |
We have been examining the mechanisms of functional regulation of growth factor receptor by N-glycans. In this study, N-glycans of ErbB4 were examined. We analyzed the site-specific glycosylation status and glycan structures of ErbB4, and found that the glycan occupancies of N146 and N448 were low as less than 50%, whereas occupancies of other sites were rather high, and those of N113 and N333 were especially high as 100%. We also found that most N-glycans on N113, N228 and N523 were oligomannose-type and those on other eight sites were complex type. We examined CHOK1 cells transfected with glycan deficient mutants of ErbB4, and found that N-glycan on N333 was involved in receptor activation: the levels and duration of heregulin-induced receptor phosphorylation were upregulated in ErbB4 N333Q mutant. The results suggested that the occupancies, structures and functions of N-glycans of ErbB4 were regulated site-specifically, and the N-glycan on N333 was involved in activation of ErbB4.
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| Free Research Field |
生化学
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| Academic Significance and Societal Importance of the Research Achievements |
増殖因子受容体はがん治療の標的であり、その制御機構を明らかにすることは社会的にも重要である。研究代表者等は糖鎖によるErbB4の制御機構を検討した。ErbB4の部位特異的な糖鎖解析を行った結果、部位によって糖鎖付加率が異なること、また糖鎖のプロセシングの程度が異なることがわかった。これらは、ErbBファミリーの全てに共通するが、METやFGFRファミリーではみられない特徴であった。一方で、機能的に重要な糖鎖は100%の付加率を示す点は、これまで調べた全ての分子に共通していた。以上の結果は受容体の糖鎖付加、そして糖鎖のプロセシングを部位特異的に決定する機構の解明につながると考えている。
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