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Lysophosphatidic Acid Receptor Family

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.

Human LPARs Members
LPAR1 LPAR2 LPAR3 LPAR4 LPAR5 LPAR6

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