論文

基本情報

氏名 中村 元直
氏名(カナ) ナカムラ モトナオ
氏名(英語) Nakamura Motonao
所属 生命科学部 生物科学科
職名 教授
researchmap研究者コード 6000014705
researchmap機関 岡山理科大学

題名

Stepwise phosphorylation of BLT1 defines complex assemblies with b-arrestin serving distinct functions.

単著・共著の別

共著

著者

Tatsumi,R., Aihara,S., Matsune,S., Aoki,J., Inoue,A., Shimizu,T., and Nakamura,M.

概要

G-protein-coupled receptors (GPCRs) utilize complex cellular systems to respond to diverse ligand concentrations. By taking BLT1, a GPCR for leukotriene B4 (LTB4), as a model, our previous work elucidated that this system functions through the modulation of phosphorylation status on two specific residues: Thr308 and Ser310. Ser310 phosphorylation occurs at a lower LTB4 concentration than Thr308, leading to a shift in ligand affinity from a high-to-low state. However, the implications of BLT1 phosphorylation in signal transduction processes or the underlying mechanisms have remained unclear. Here, we identify the sequential BLT1-engaged conformations of b-arrestin and subsequent alterations in signal transduction. Stimulation of the high-affinity BLT1 with LTB4 induces phosphorylation at Ser310 via the ERK1/2-GRK pathway, resulting in a b-arrestin-bound low-affinity state. This configuration, referred to as the “low-LTB4-induced complex,” necessitates the finger loop region and the phosphoinositide-binding motif of b-arrestins to interact with BLT1 and deactivates the ERK1/2 signaling. Under high LTB4 concentrations, the low-affinity BLT1 again binds to the ligand and triggers the generation of the low-LTB4-induced complex into a different form termed “high-LTB4-induced complex.” This change is propelled by The308-phosphorylation-dependent basal-phosphorylation by PKCs. Within the high-LTB4-induced complex, b-arrestin adapts a unique configuration that involves additional N domain interaction to the low-affinity BLT1 and stimulates the PI3K/AKT pathway. We propose that the stepwise phosphorylation of BLT1 defines the formation of complex assemblies, wherein b-arrestins perform distinct functions.

発表雑誌等の名称

The FASEB Journal

出版者

DOI:10.1096/fj.202301440R

開始ページ

終了ページ

発行又は発表の年月

2023/10

査読の有無

有り

招待の有無

無し

記述言語

英語

掲載種別

研究論文(学術雑誌)

ISSN

ID:DOI

DOI:10.1096/fj.202301440R

ID:NAID(CiNiiのID)

ID:PMID

URL

JGlobalID

arXiv ID

ORCIDのPut Code

DBLP ID