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 journalArticle

2 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
Pages (from-to)e402
JournalExperimental & molecular medicine
Volume49
Issue number11
DOIs
Publication statusPublished - 2017 Nov 24

Fingerprint

Leukotriene B4 Receptors
Polymorphism
Cell Movement
Genes
Single Nucleotide Polymorphism
Ligands
Nucleotides
G-Protein-Coupled Receptors
Therapeutic Uses
Reactive Oxygen Species
Asthma
Chemical activation
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Leukotriene B4 receptor 2 gene polymorphism (rs1950504, Asp196Gly) leads to enhanced cell motility under low-dose ligand stimulation. / Jang, Jae Hyun; Wei, Jun Dong; Kim, Minsup; Kim, Joo Young; Cho, Art E.; Kim, Jae-Hong.

In: Experimental & molecular medicine, Vol. 49, No. 11, 24.11.2017, p. e402.

Research output: Contribution to journalArticle

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