LTB4R2 Membrane Protein Introduction

Introduction of LTB4R2

LTB4R2, encoded by LTB4R2 gene, belongs to G-protein coupled receptor family which possesses seven transmembrane regions. It is one of two receptors for leukotriene B4 (LTB4), with far lower affinity than the other LTB4 receptor 1 (LTB4R1). Moreover, the pattern expression of the two receptors is different. LTB4R1 is predominantly expressed in peripheral leukocytes, while LTB4R2 is expressed more ubiquitously, with the highest level in the skin, spleen, bone marrow and lymphocytes. The two receptors are both associated with pathologic inflammation.

Function of LTB4R2 Membrane Protein

LTB4R2 is a receptor of LBT4 which is a potent leukocyte activator and chemoattractant. The activated LTB4R2 by binding to LBT4 stimulates the activation of G proteins and transiently elevated cytosolic calcium ion concentrations, resulting in the activation of calcium-activated intracellular signaling molecules. It also stimulates cells to activate Extracellular signal-regulated kinases (ERKs), Protein kinase B (also known as Akt), c-Jun N-terminal kinases (JNKs), Janus kinase (JAK)-STAT protein. Like LTB4R1, LTB4R2 is also involved in the regulation of inflammation and allergic responses. LTB4R2 knockout in mice reduces ovalbumen-induced allergic airway eosinophilia and Interleukin 13 (IL-13) content in their bronchoalveolar lavage fluid compared with wild-type mice. And compared to wild-type or LTB4R1 knockout mice, LTB4R2 knockout mice exhibit more severe colitis inflammation, increased mRNA expression for the pro-inflammatory cytokines (i.e. interferon-γ, IL1B), and decreased colon mucosa integrity and barrier function. Studies have shown that LTB4R2 is associated with many pathological conditions, such as allergic airways diseases, inflammation, prostate cancer, urinary bladder cancer, breast cancer, ovarian cancer, pancreatic cancer, colon cancer, esophageal cancer.

Fig.1 Schematic representation of leukotriene B4 signaling events augmenting osteoclastogenesis. (Dixit, 2014)

Application of LTB4R2 Membrane Protein in Literature

1. Park J., et al. BLT2, a leukotriene B4 receptor 2, as a novel prognostic biomarker of triple-negative breast cancer. BMB Reports. 2018, 51(8):373-377. PubMed ID: 29898809
   
   

   In this review, authors propose that LTB4R2 is associated with the phenotypes of triple-negative breast cancer (TNBC) cells, including invasion, metastasis, and survival. And anti-BLT2 strategies could facilitate the development of new therapies used for TNBC.

2. Liu M., et al. Leukotriene B4 receptor 2 regulates the proliferation, migration and barrier integrity of bronchial epithelial cells. Journal of Cellular Physiology. 2018, 233(8):6117-6124. PubMed ID: 29323699
   
   

   The results suggest that BLT2 plays a key role in the airway epithelial barrier integrity and BLT2 agonists are potential therapeutic agents for asthma treatment.

3. Jang J.H., et al. Leukotriene B4 receptor 2 gene polymorphism (rs1950504, Asp196Gly) leads to enhanced cell motility under low-dose ligand stimulation. Experimental & Molecular Medicine. 2017, 49(11):e402. PubMed ID: 29170475
   
   

   The findings show that D196G in BLT2 enhances ligand sensitivity, thereby increasing cell motility in response to low-dose ligand stimulation.

4. Zinn S., et al. The leukotriene B4 receptors BLT1 and BLT2 form an antagonistic sensitizing system in peripheral sensory neurons. Journal of Biological Chemistry. 2017, 292(15):6123-6134. PubMed ID: 28242764
   
   

   The article shows that the two leukotriene B4 receptors have opposing roles in the sensitization of peripheral sensory neurons forming a self-restricting system.

5. Luo L., et al. A synthetic leukotriene B4 receptor type 2 agonist accelerates the cutaneous wound healing process in diabetic rats by indirect stimulation of fibroblasts and direct stimulation of keratinocytes. Journal of Diabetes & Its Complications. 2017, 31(1):13-20. PubMed ID: 27742551
   
   

   The study shows that the BLT2 agonist CAY10583 (CAY) can promote keratinocyte migration and indirectly enhances fibroblast proliferation by increasing keratinocyte production of TGF-β1 and bFGF, accelerating wound closure.

LTB4R2 Preparation Options

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Reference

1. Dixit N, et al. (2014). Leukotriene B4 activates intracellular calcium and augments human osteoclastogenesis. Arthritis Research & Therapy. 16(6), 496.

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