LPAR2 Membrane Protein Introduction

Introduction of LPAR2

LPAR2, encoded by LPAR2 gene, is a G-protein coupled receptor that belongs to the endothelial differentiation gene (EDG) family of receptors. The receptor is about 39.1 kDa and consists of 351 amino acid residues. It has seven transmembrane regions, three numbered extracellular and intracellular loops. LPAR2 mRNA is expressed in a variety of tissues including human testis, leukocytes, spleen, thymus, pancreas, and bone marrow. Most researches indicate that LPAR2 is involved in the regulation of cell survival, proliferation, and migration.

Function of LPAR2 Membrane Protein

LPAR2 is activated via interaction with its ligands, lysophosphatidic acid (LPA), and transduces extracellular signals into intracellular downstream signaling molecules, such as phosphatidylinositol 3-kinase, phospholipase C, Ca²⁺, Ras, Rac, and Rho. The activated LPAR2 is involved in the regulation of cellular responses including cell growth, differentiation, survival and migration. It has been indicated that LPAR2 plays an essential role in the progression of many cancers, acting as a potential predictor and prognostic biomarker for tumors. LPAR2 may be associated with the production of estrogens and androgens, involved in the progression of endometrial carcinoma and ovarian endometriotic cysts. The high LPAR2 levels are associated with the poor outcomes of breast cancer with shorter overall survival. However, the inhibition of LPAR2 can suppress the migration of ovarian cancer cells. These also suggest that LPAR2 can be considered as a promising therapeutic target for many types of tumor treatment.

Fig.1 The mechanism of LPA signaling transduction. (Knowlden, 2013)

Application of LPAR2 Membrane Protein in Literature

1. Kowalczyk-Zieba I., et al. LPAR2 and LPAR4 are the main receptors responsible for LPA actions in ovarian endometriotic cysts. Reproductive Sciences. 2018. PubMed ID: 29621954
   
   

   The study indicates that the high production of LPAR2 and LPAR4 is observed in ovarian endometriotic cysts and positive correlations of both these receptors with the expression of E2 and P4 receptors. Hence, LPAR2 and LPAR4 are mainly responsible for LPA activation in ovarian endometriotic cysts and those receptors may serve as the promising biomarkers of the endometriotic cysts.

2. Takahashi K., et al. Involvement of LPA signaling via LPA receptor-2 in the promotion of malignant properties in osteosarcoma cells. Experimental Cell Research. 2018, 15;369(2):316-324. PubMed ID: 29859140
   
   

   The study shows that LPA-LPAR2 signaling pathway may promote acquisition of malignant properties during tumor progression in MG-63 cells.

3. Park J., et al. LPA-induced migration of ovarian cancer cells requires activation of ERM proteins via LPA1 and LPA2. Cellular Signalling. 2018, 44:138-147. PubMed ID: 29329782
   
   

   The study reveals that LPA1 and LPA2 induce phosphorylation of ezrin/radixin/moesin (ERM) proteins that are membrane-cytoskeleton linkers involved in cytoskeletal reorganization and formation of membrane protrusions in OVCAR-3 cells. Besides, the silencing of LPA1 and LPA2 can abolish OVCAR-3 cells migration, suggesting that these receptors could provide the potential therapeutic targets for metastatic ovarian cancer.

4. Wasniewski T., et al. Altered expression of lysophosphatidic acid receptors, in association with the synthesis of estrogens and androgens in type 1 endometrial cancer biology. Gynecological Endocrinology. 2018, 34(5):422-427. PubMed ID: 29182028
   
   

   The study indicates that LPAR1 and LPAR2 are positively associated with proliferation SRD5A2 in endometrial carcinoma (EC) tissue, suggesting that intratumoral estrogen metabolism and synthesis are pivotal in endometrial carcinoma progression, with the involvement of LPA in this process.

5. Yang B., et al. Elevated plasma levels of lysophosphatidic acid and aberrant expression of lysophosphatidic acid receptors in adenomyosis. Bmc Womens Health. 2017, 17(1):118. PubMed ID: 29178922
   
   

   The study shows that elevated plasma levels of LPA and aberrant expression of LPA receptors in the endometria may be associated with the development of adenomyosis.

LPAR2 Preparation Options

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Reference

1. Knowlden S and Georas S. (2013). LPAR2 (lysophosphatidic acid receptor 2). Atlas of Genetics and Cytogenetics in Oncology and Haematology. 17(4), 259-65.

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