2021 Fiscal Year Final Research Report
A new ligand for ALK and its activation mechanism
| Project/Area Number |
19H03415
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
坂元 一真 名古屋大学, 医学系研究科, 准教授 (60612801)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | ALK / 受容体型チロシンキナーゼ / デルマタン硫酸 / 神経軸索再生 / 受容体型チロシンフォスファターゼ |
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| Outline of Final Research Achievements |
The principal investigators searched for a new kinase that opposes the receptor-type tyrosine phosphatase PTPRσ, which inhibits neuroaxonal regeneration, and discovered that ALK (anaplastic lymphoma kinase) promotes neuroaxonal regeneration. In addition, the study found that dermatan sulfate (DS), a sulfated glycan, strongly activates ALK and promotes neuroaxonal regeneration in an ALK-dependent manner. In the current study, we demonstrated that DS has sufficient affinity for ALK and induces its clustering. Furthermore, we identified a group of molecules interacting with ALK and PTPRσ by the proximity-dependent labeling method BioID. The results revealed that there is a group of substrate molecules common to these two enzymes with opposing functions. Future studies can be developed on the physiological significance of these molecular switches.
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| Free Research Field |
生化学
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| Academic Significance and Societal Importance of the Research Achievements |
受容体型チロシンキナーゼと受容体型テロシンキナーゼと受容体型チロシンフォスファターゼのクロストークは予想はされてきたが、その具合を示す例は少ない。本研究によって光が見えはじめたALKとPTPRσのクロストークは、新しい生命制御機構の1つを提示するものである。既に研究代表者らは、神経系でその生物学的意味についてもアドレスできる立場にあるが、両者は、神経発達・回路形成・再編などに関わる可能性があり、関連する疾病の病態解明、治療法開発につながる可能性がある。
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