LPAR5 Membrane Protein Introduction

Introduction of LPAR5

LPAR5, encoded by LPAR5 gene, is a member of seven transmembrane G-protein coupled receptor family and couples to G_12/13 and G_q/11. It is one of six LAP receptor subtypes (LPA1-6) and has about 22% homology to LPA1-3 and about 35% homology to LPAR4. LPAR5 is highly expressed in spleen, and to a lesser degree in heart, small intestine, placenta, colon, and liver. Most studies have shown that LPAR5 can act as the prognostic and therapeutic target for many types of cancers due to its functions in the procession of cancers.

Function of LPAR5 Membrane Protein

Activated LPAR5 by LPA promotes adenylyl cyclase activities via stimulating G proteins activation, resulting in the changes of intracellular signaling molecules, such as cAMP accumulation and intracellular calcium levels, thereby regulating many cell biological responses. It is reported that LPA5 is observed in the early embryonic mouse forebrain, rostral midbrain, and hindbrain, indicating that LPA5 may play a role in brain development. And it was found LPA interacting with LPA5 can inhibit melanoma cells migration via cAMP-protein kinase A pathway. Moreover, LPA also induces a motile and pro-inflammatory microglial phenotype via LPA 5/protein kinase D-dependent pathways. A recent study indicates that LPA-LPA5 axis is also associated with intestine Na⁺/H⁺ exchanger 3 (NHE3) activation which recruits NHE3 to the microvilli. In addition, many studies have revealed that LPA5 can act as the prognostic and therapeutic target for many cancers due to its role in the pathological processes of cancers, including thyroid cancer, EBV-associated nasopharyngeal carcinoma, pancreatic cancer, melanoma.

Fig.1 Diverse pathways of lysophosphatidic acid (LPA) signal transduction. (Gong, 2012)

Application of LPAR5 Membrane Protein in Literature

1. Jenkin K.A., et al. The expression of lysophosphatidic acid receptor 5 is necessary for the regulation of intestinal Na⁺/H⁺ exchanger 3 by lysophosphatidic acid in vivo. American Journal of Physiology Gastrointestinal and Liver Physiology. 2018, 315(4):G433-G442. PubMed ID: 29792531
   
   

   The in vivo study shows that LPA-LPA5 axis is associated with intestine Na⁺/H⁺ exchanger 3 (NHE3) activation that is involved in the transportation of NHE3 from the terminal web to microvilli.

2. Tang J., et al. Bioinformatic analysis and identification of potential prognostic microRNAs and mRNAs in thyroid cancer. Peerj. 2018, 6:e4674. PubMed ID: 29740512
   
   

   The authors identify that LPAR5, miR-184, miR-146b and miR-509-3 can be considered as the prognostic and therapeutic targets for thyroid cancer via multivariate analysis.

3. Tsukahara R., et al. LPA5 signaling is involved in multiple sclerosis-mediated neuropathic pain in the cuprizone mouse model. Journal of Pharmacological Sciences. 2018, 136(2):93-96. PubMed ID: 29409686
   
   

   The study shows that LPA5 signaling is associated with the mediation of potential mechanisms involving neuropathic pain following demyelination in the brain.

4. Kawamoto Y., et al. Identification of potent lysophosphatidic acid receptor 5 (LPA5) antagonists as potential analgesic agents. Bioorg Med Chem. 2018, 26(1):257-265. PubMed ID: 29208511
   
   

   The research finds that LPA5 antagonist, 7e exerts an effective analgesic effect in a chronic constriction injury rat model, suggesting that 7e is a potential analgesic agent.

5. Plastira I., et al. Lysophosphatidic acid via LPA-receptor 5/protein kinase D-dependent pathways induces a motile and pro-inflammatory microglial phenotype. Journal of Neuroinflammation. 2017, 14(1):253. PubMed ID: 29258556
   
   

   The study shows that inflammatory LPA levels increase the migratory response of microglia and promote a pro-inflammatory phenotype via the LPAR5/PKD axis. Blockage the signaling axis could suppress microglial migration, decrease microglial cytotoxicity, and inhibit the expression and secretion of pro-inflammatory mediators.

LPAR5 Preparation Options

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Reference

1. Gong Y L, et al. (2012). Expression of lysophosphatidic acid receptors and local invasiveness and metastasis in Chinese pancreatic cancers. Current Oncology. 19(Suppl 2), eS15–eS21.

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