Leukotriene B4 receptor 2 gene polymorphism (Rs1950504, Asp196Gly) leads to enhanced cell motility under low-dose ligand stimulation

Jae Hyun Jang, Jun Dong Wei, Minsup Kim, Joo Young Kim, Art E. Cho, Jae Hong Kim

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Recently, single-nucleotide polymorphisms (SNPs) in G-protein-coupled receptors (GPCRs) have been suggested to contribute to physiopathology and therapeutic effects. Leukotriene B4 receptor 2 (BLT2), a member of the GPCR family, plays a critical role in the pathogenesis of several inflammatory diseases, including cancer and asthma. However, no studies on BLT2 SNP effects have been reported to date. In this study, we demonstrate that the BLT2 SNP (rs1950504, Asp196Gly), a Gly-196 variant of BLT2 (BLT2 D196G), causes enhanced cell motility under low-dose stimulation of its ligands. In addition, we demonstrated that Akt activation and subsequent production of reactive oxygen species (ROS), both of which act downstream of BLT2, are also increased by BLT2 D196G in response to low-dose ligand stimulation. Furthermore, we observed that the ligand binding affinity of BLT2 D196G was enhanced compared with that of BLT2. Through homology modeling analysis, it was predicted that BLT2 D196G loses ionic interaction with R197, potentially resulting in increased agonist-receptor interaction. To the best of our knowledge, this report is the first to describe a SNP study on BLT2 and shows that BLT2 D196G enhances ligand sensitivity, thereby increasing cell motility in response to low-dose ligand stimulation.

Original languageEnglish
Article numbere402
JournalExperimental and Molecular Medicine
Volume49
Issue number11
DOIs
Publication statusPublished - 2017 Nov 3

Bibliographical note

Funding Information:
This work was supported by Bio and Medical Technology Development Program grants (2012M3A9C1053532 and 2017M3A9D8063317) and a Mid-Career Researcher Program grant (2017R1A2B4002203) through the National Research Foundation (NRF) funded by the Ministry of Science, Information and Communication Technologies (ICT) and Future Planning of the Republic of Korea. This work was also supported by Basic Science Research (2015R1D1A1A01057757) through the NRF funded by the Ministry of Education, BK21 Plus Program (College of Life Sciences and Biotechnology, Korea University) and by a Korea University Grant.

Publisher Copyright:
© The Author(s) 2017.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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