The lysophosphatidic acid receptors (LPARs) are a group of G protein-coupled receptors for lysophosphatidic acid (LPA), a bioactive lipid mediator with wide distribution on almost all types of mammalian cells and diverse physiological and pathological actions. LPARs are associated with phosphatidylinositol 3-kinase (PI3K)–AKT pathway activation. When binding to its receptors, LPA can efficiently activate AKT phosphorylation in a multitude of cell types, and the interplay line LPA-its receptors-PI3K-AKT contributes to the regulation of cell survival, migration, proliferation and confers chemotherapy-resistance in certain cancers. Until now, 6 types of LPARs are discovered, namely LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, LPAR6. All LPARs are rhodopsin-like 7-TM proteins that usually trigger responses from multiple heterotrimeric G-proteins, leading to diverse outcomes. LPAR1-3 are also vested in the endothelial differentiation, G-protein-coupled (EDG) family, because they were first identified as orphan GPCRs involved in endothelial gene differentiation in human umbilical vein endothelial cells. Sharing little homology with the EDG family, LPR4-6 are defined as non-EDG family receptors.
Here show 6 types of LPARs in humans. By the activation of Gα pathway, LPAR1 carries out downstream signaling, including cytoskeletal organization and cell migration, cell proliferation, apoptosis, cell survival and Ca2+ homeostasis. LPAR2 mostly activates the same pathways as triggered by LPAR1. LPAR3 can regulate Ca2+ homeostasis and cAMP levels by the activation of PLC and MAPK. LPAR4 is the only receptor that activates adenylyl cyclase and thus causes a rise in cAMP levels in cells. LPAR5 has been implicated in the regulation of water absorption, Ca2+ mobilization and increase in cAMP levels. LPAR6 was identified as an LPA-binding P2Y5 receptor vital for hair growth and quickly confirmed as an RHO-activating LPA receptor.
Aided by cutting-edge Magic™ membrane protein production platform, Creative Biolabs is proud to offer the preparation of these targets in required formats using various strategies, such as detergent micelles, proteoliposomes, nanodiscs, lipoparticles, polymers, stable cell line.
Meanwhile, our Magic™ membrane protein antibody discovery platform can help to discover antibodies against these targets, even fully humanized antibodies, by various approaches including hybridoma technology, phage display technology, etc. We also present DNA immunization service for anti-membrane protein antibody development. Please feel free to contact us for more information.