Phosphorylations of BLT1 receptor are necessary for sufficient cell responses at high concentration of leukotriene B4
Project/Area Number |
17K08294
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | Okayama University of Science |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | ロイコトリエンB4 / BLT1 / リン酸化 / ユビキチン修飾 / βアレスチン / G蛋白質共役型受容体 / GPCR / Gタンパク質共役型受容体 / 情報伝達 / ロイコトリエンB4 / リン酸化修飾 / 好中球 / 炎症 / Gタンパク質共役型受容体タンパク質共役型受容体 / シグナル伝達 / 白血球 |
Outline of Final Research Achievements |
LTB4 receptor type 1 (BLT1) is abundantly expressed in immune cells and plays crucial roles in various inflammatory diseases. We determined two types of BLT1 phosphorylation, basal and ligand-induced, in the C-terminus of human BLT1 using the Phos-tag SDS-PAGE. Ligand-induced phosphorylation occurred at different LTB4 concentrations, and this modification facilitated basal phosphorylation. Because neutrophils migrate through the LTB4 gradient toward inflammatory sites, the degree of phosphorylation could be enhanced in parallel with an increase in LTB4. At high concentrations of LTB4, deficiencies in these two types of phosphorylation impaired chemotaxis and β-hexosaminidase release in CHO-K1 and RBL-2H3 cells, respectively. These results suggest that an LTB4 gradient around inflammatory regions boosts BLT1 phosphorylation in a stepwise manner to facilitate the precise migration of phagocytic and immune cells, and the initiation of local responses, including degranulation.
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Academic Significance and Societal Importance of the Research Achievements |
炎症時、局所で産生されたLTB4は血中に放出され、好中球はこの際のリガンド濃度勾配を頼りに局所へ向かう。これまでこの濃度勾配は遊走の方向指示のみに重要とされてきたが、我々はこれに新たな意義を加える。BLT1を介して好中球に局所応答の開始時期を伝える意義である。低親和性化したBLT1が濃度勾配の中で再活性化されうる高いLTB4濃度に到達することで、この低親和性型を介して高親和性型とは異なる情報伝達が作動し、局所応答が開始されるという考え方である。この仕組みは全く新奇なシグナル伝達調節の発見である。
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Stepwise phosphorylation of leukotriene B4 receptor 1 defines cellular responses to leukotriene B4.2018
Author(s)
Nakanishi,Y., Tan,M., Ichiki,T., Inoue,A. Yoshihara,J., Maekawa,N., Takenoshita.I., Yanagida,K., Yamahira,S., Yamaguchi,S., Aoki,J. Nagamune,T., Yokomizo,T., Shimizu,T., and Nakamura,M
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Journal Title
Science Signaling
Volume: 11 (544)
Issue: 544
Pages: 5390-5390
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Microfluidic preparation of anchored cell membrane sheets for in vitro analyses and manipulation of the cytoplasmic face2017
Author(s)
Izuta,S., Yamaguchi,S., Misawa,R., Yamahira,S., Tan,M., Kawahara,M., Suzuki,T., Takagi,T., Sato,K., Nakamura,M., Nagamune,T. and Okamoto,A.
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Journal Title
Sci. Rep.
Volume: 7:14962
Issue: 1
Pages: 14962-14962
DOI
Related Report
Peer Reviewed / Open Access
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