Research Project
Grant-in-Aid for Scientific Research (C)
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.
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。
All 2020 2019 2018 2017
All Journal Article (7 results) (of which Peer Reviewed: 7 results, Open Access: 4 results, Acknowledgement Compliant: 1 results) Presentation (24 results) (of which Invited: 2 results) Book (1 results)
Encyclopedia of Molecular Pharmacology
Volume: 11 March Pages: 1-10
10.1007/978-3-030-21573-6_87-1
Science Signaling
Volume: 11 (544) Issue: 544 Pages: 5390-5390
10.1126/scisignal.aao5390
J.Clinical Investigation
Volume: 128 Issue: 7 Pages: 2691-2701
10.1172/jci97946
ournal of Bioscience and Bioengineering
Volume: 印刷中 Issue: 3 Pages: 30031-30066
10.1016/j.jbiosc.2018.03.012
40021667194
Nature Chemical Biology
Volume: 14 Issue: 3 Pages: 262-269
10.1038/nchembio.2547
Lab on a Chip
Volume: 印刷中 Issue: 11 Pages: 1933-1938
10.1039/c7lc00198c
Sci. Rep.
Volume: 7:14962 Issue: 1 Pages: 14962-14962
10.1038/s41598-017-14737-7
