Topic
LPAR3
About: LPAR3 is a research topic. Over the lifetime, 90 publications have been published within this topic receiving 13128 citations. The topic is also known as: EDG7 & Edg-7.
Papers published on a yearly basis
Papers
TL;DR: Generation of LP receptor-null animals has allowed rigorous examination of receptor-mediated physiological functions in vivo and has identified new functions for LP receptor signaling, and efforts to develop LP receptor subtype-specific agonists/antagonists are in progress.
Abstract: ▪ Abstract Lysophospholipids (LPs), such as lysophosphatidic acid and sphingosine 1-phosphate, are membrane-derived bioactive lipid mediators. LPs can affect fundamental cellular functions, which include proliferation, differentiation, survival, migration, adhesion, invasion, and morphogenesis. These functions influence many biological processes that include neurogenesis, angiogenesis, wound healing, immunity, and carcinogenesis. In recent years, identification of multiple cognate G protein-coupled receptors has provided a mechanistic framework for understanding how LPs play such diverse roles. Generation of LP receptor-null animals has allowed rigorous examination of receptor-mediated physiological functions in vivo and has identified new functions for LP receptor signaling. Efforts to develop LP receptor subtype-specific agonists/antagonists are in progress and raise expectations for a growing collection of chemical tools and potential therapeutic compounds. The rapidly expanding literature on the LP re...
811 citations
TL;DR: Vzg-1 provides a link between extracellular LPA and the activation of LPA- mediated signaling pathways through a single receptor and will allow new investigations into LPA signaling both in neural and nonneural systems.
Abstract: Neocortical neuroblast cell lines were used to clone G-protein-coupled receptor (GPCR) genes to study signaling mechanisms regulating cortical neurogenesis. One putative GPCR gene displayed an in situ expression pattern enriched in cortical neurogenic regions and was therefore named ventricular zone gene-1 (vzg-1). The vzg-1 cDNA hybridized to a 3.8-kb mRNA transcript and encoded a protein with a predicted molecular mass of 41-42 kD, confirmed by Western blot analysis. To assess its function, vzg-1 was overexpressed in a cell line from which it was cloned, inducing serum-dependent "cell rounding." Lysophosphatidic acid (LPA), a bioactive lipid present in high concentrations in serum, reproduced the effect seen with serum alone. Morphological responses to other related phospholipids or to thrombin, another agent that induces cell rounding through a GPCR, were not observed in vzg-1 overexpressing cells. Vzg-1 overexpression decreased the EC50 of both cell rounding and Gi activation in response to LPA. Pertussis toxin treatment inhibited vzg-1-dependent LPA-mediated Gi activation, but had no effect on cell rounding. Membrane binding studies indicated that vzg-1 overexpression increased specific LPA binding. These analyses identify the vzg-1 gene product as a receptor for LPA, suggesting the operation of LPA signaling mechanisms in cortical neurogenesis. Vzg-1 therefore provides a link between extracellular LPA and the activation of LPA-mediated signaling pathways through a single receptor and will allow new investigations into LPA signaling both in neural and nonneural systems.
775 citations
TL;DR: It is found that thrombin activation of platelets prelabelled with [32P]Pi results in the rapid release of newly formed LPA into the extracellular environment, suggesting that LPA is produced during blood clotting.
Abstract: Lysophosphatidic acid (LPA) is a water-soluble phospholipid with hormone-like and growth-factor-like activities. LPA activates a putative G-protein-coupled receptor in responsive cells, but the natural source of exogenous LPA is unknown. Here we show that LPA is present in mammalian serum in an active form (bound to albumin) at concentrations of 1-5 microM, but is not detectable in platelet-poor plasma, suggesting that LPA is produced during blood clotting. We find that thrombin activation of platelets prelabelled with [32P]Pi results in the rapid release of newly formed [32P]LPA into the extracellular environment. We conclude that LPA is a novel platelet-derived lipid mediator that may play a role in inflammatory and proliferative responses to injury.
688 citations
TL;DR: The potential of LPA receptor subtypes and related signaling mechanisms to provide novel therapeutic targets are underscored.
661 citations
TL;DR: Competition binding and reporter gene assays showed that p2y9/GPR23 preferred structural analogs of LPA with a rank order of 1-oleoyl- > 1-stearoyl < 1-palmitoyl • 1-myristoyl | 1-alkyl- >1-alkenyl-LPA, and phylogenetic analysis shows that p 2y9 / GPR23 is far distant from the Edg family.
593 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 2 |
| 2020 | 1 |
| 2019 | 6 |
| 2018 | 7 |
| 2017 | 4 |
| 2016 | 5 |