Introduction of LPAR1
LPAR1, encoded by LPAR1 gene, is a member of G-protein coupled receptor family. It possesses seven transmembrane domains, three numbered extracellular and intracellular loops. The receptor is homological to other 5 lysophosphatidic acid receptor subtypes (LPAR2 - LPAR6). They have a range of effects on different cell type, including cell proliferation, differentiation, apoptosis and invasion. Moreover, some studies have shown that the pathological process of tumors is associated with the LPARs.
|Basic Information of LPAR1|
|Protein Name||Lysophosphatidic acid receptor 1|
|Aliases||EDG2, LPA1, VZG1, GPR26, edg-2, vzg-1, Gpcr26, Mrec1.3, rec.1.3|
|Organism||Homo sapiens (Human)|
Function of LPAR1 Membrane Protein
LPAR1 is a receptor for lysophosphatidic acid (LPA). Activated LPAR1 via binding to its ligands could inhibit the production of intracellular second messager cAMP initiating cell signaling transduction. Depending on the cell types, the activated receptor can mediate multiple biologic functions, including proliferation, platelet aggregation, smooth muscle contraction, inhibition of neuroblastoma cell differentiation, chemotaxis, and tumor cell invasion. Most studies have shown that LPAR1 is associated with the pathological process of a number of diseases, including Sjögren's syndrome, diabetic nephropathy, coronary heart disease, and tumor proliferation as well as migration. The missense mutations of LPAR1 is observed in many cancer tissues. The cross-talk between LPAR1 and receptor tyrosine kinases (RTKs) could mediate lung epithelial cell migration. Cross-talk between LPAR1 and the epidermal growth factor (EGF) receptor could promote cell proliferation in prostate cancer. Besides, LPAR1 antagonists may be the promising therapeutic drugs in many diseases. It has been proved that the inhibition of LPAR can relieve Sjögren's syndrome in nonobese diabetic mice, inhibits diabetic nephropathy in db/db mice, and attenuates atherosclerosis development in LDL-receptor deficient mice.
Fig.1 Structure of the LPAR1. (Murph, 2010)
Application of LPAR1 Membrane Protein in Literature
The research shows that the hypoxic tumor microenvironment stimulates cell invasion and metastasis through the mediation of LPA1-EGFR signaling pathway, suggesting that LPA1-EGFR signaling pathway can be used as the target to suppress tumor cells metastasis.
The study indicates that LPA and LPA1 play an important role in the regulation of urethral tonus and prostate cell proliferation. The LPA1 antagonist ASP6432 is a potential therapeutic agent for lower urinary tract symptoms associated with benign prostate hyperplasia.
The study indicates that LPA1 receptor antagonist SAR100842 is well tolerated in patients with systemic sclerosis (SSc). And a baseline Rodnan skin score (MRSS) improves during the study. Besides, LPA related genes are reduced in the skin of SAR100842 group, suggesting LPA1 targets the engagement.
The study indicates that LPA1 and LPA6 may be involved in regulation of the colony formation activity in DLD1 cells treated with anticancer drugs.
The study suggests that LPA1 plays a significant role in the maintenance of epithelial barrier function in the intestine via regulation of apical junction integrity.
LPAR1 Preparation Options
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