International union of pharmacology. XXXIV. Lysophospholipid receptor nomenclature (original) (raw)
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Lysophospholipid (S1P) receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
IUPHAR/BPS Guide to Pharmacology CITE
Sphingosine 1-phosphate (S1P) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid receptors [70]) are activated by the endogenous lipid sphingosine 1-phosphate (S1P). Originally cloned as orphan members of the endothelial differentiation gene (edg) family, current gene names have been designated as S1P1R through S1P5R [52]. S1PRs, particularly S1P1, are expressed throughout all mammalian organ systems. Ligand delivery occurs via two known carriers (or "chaperones"): albumin and HDL-bound apolipoprotein M (ApoM), the latter of which elicits biased agonist signaling by S1P1 in multiple cell types [15, 39]. The five S1PRs, two chaperones, and active cellular metabolism have complicated analyses of receptor ligand binding in native systems. Signaling pathways and physiological roles have been characterized through radioligand binding in heterologous expression systems, targeted deletion of the different S1PRs, and most recently, mouse models tha...
Lysophospholipid receptors: Signalling, pharmacology and regulation by lysophospholipid metabolism
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2007
The lysophospholipids, sphingosine-1-phosphate (S1P), lysophosphatidic acid (LPA), sphingosylphosphorylcholine (SPC) and lysophosphatidylcholine (LPC), activate diverse groups of G-protein-coupled receptors that are widely expressed and regulate decisive cellular functions. Receptors of the endothelial differentiation gene family are activated by S1P (S1P 1-5 ) or LPA (LPA 1-3 ); two more distantly related receptors are activated by LPA (LPA 4/5 ); the GPR 3/6/12 receptors have a high constitutive activity but are further activated by S1P and/or SPC; and receptors of the OGR1 cluster (OGR1, GPR4, G2A, TDAG8) appear to be activated by SPC, LPC, psychosine and/or protons. G-protein-coupled lysophospholipid receptors regulate cellular Ca 2+ homoeostasis and the cytoskeleton, proliferation and survival, migration and adhesion. They have been implicated in development, regulation of the cardiovascular, immune and nervous systems, inflammation, arteriosclerosis and cancer. The availability of S1P and LPA at their G-protein-coupled receptors is regulated by enzymes that generate or metabolize these lysophospholipids, and localization plays an important role in this process. Besides FTY720, which is phosphorylated by sphingosine kinase-2 and then acts on four of the five S1P receptors of the endothelial differentiation gene family, other compounds have been identified that interact with more ore less selectivity with lysophospholipid receptors.
Lysophospholipid (LPA) receptors in GtoPdb v.2021.3
IUPHAR/BPS Guide to Pharmacology CITE, 2021
Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid Receptors [55, 19, 82, 129]) are activated by the endogenous phospholipid LPA. The first receptor, LPA1, was identified as ventricular zone gene-1 (vzg-1) [40], This discovery represented the beginning of the de-orphanisation of members of the endothelial differentiation gene (edg) family, as other LPA and sphingosine 1-phosphate (S1P) receptors were found. Five additional LPA receptors (LPA2,3,4,5,6) have since been identified [82] and their gene nomenclature codified for human LPAR1, LPAR2, etc. (HUGO Gene Nomenclature Committee, HGNC) and Lpar1, Lpar2, etc. for mice (Mouse Genome Informatics Database, MGI) to reflect species and receptor function of their corresponding proteins. The crystal structure of LPA1 is solved and indicates that LPA accesses the extracellular binding pocket, consistent with its proposed delivery via autotaxin [13]. These studies have also implic...
Lysophospholipid (LPA) receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
IUPHAR/BPS Guide to Pharmacology CITE
Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid Receptors [50, 18]) are activated by the endogenous phospholipid LPA. The first receptor, LPA1, was identified as ventricular zone gene-1 (vzg-1) [38], leading to deorphanisation of members of the endothelial differentiation gene (edg) family as other LPA receptors along with sphingosine 1-phosphate (S1P) receptors. Additional LPA receptor GPCRs were later identified. Gene names have been codified as LPAR1, etc. to reflect the receptor function of proteins. The crystal structure of LPA1 was solved and demonstrates extracellular LPA access to the binding pocket, consistent with proposed delivery via autotaxin [12]. These studies have also implicated cross-talk with endocannabinoids via phosphorylated intermediates that can also activate these receptors. The identified receptors can account for most, although not all, LPA-induced phenomena in the literature, indicating that ...
L YSOPHOSPHOLIPID R ECEPTORS : Signaling and Biology
Annual Review of Biochemistry, 2004
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 receptors is herein reviewed.
Lysophospholipids and their receptors in the central nervous system
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2013
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), two of the best-studied lysophospholipids, are known to influence diverse biological events, including organismal development as well as function and pathogenesis within multiple organ systems. These functional roles are due to a family of at least 11 G protein-coupled receptors (GPCRs), named LPA 1-6 and S1P 1-5 , which are widely distributed throughout the body and that activate multiple effector pathways initiated by a range of heterotrimeric G proteins including G i/o , G 12/13 , G q and G s , with actual activation dependent on receptor subtypes. In the central nervous system (CNS), a major locus for these signaling pathways, LPA and S1P have been shown to influence myriad responses in neurons and glial cell types through their cognate receptors. These receptor-mediated activities can contribute to disease pathogenesis and have therapeutic relevance to human CNS disorders as demonstrated for multiple sclerosis (MS) and possibly others that include congenital hydrocephalus, ischemic stroke, neurotrauma, neuropsychiatric disorders, developmental disorders, seizures, hearing loss, and Sandhoff disease, based upon the experimental literature. In particular, FTY720 (fingolimod, Gilenya, Novartis Pharma, AG) that becomes an analog of S1P upon phosphorylation, was approved by the FDA in 2010 as a first oral treatment for MS, validating this class of receptors as medicinal targets. This review will provide an overview and update on the biological functions of LPA and S1P signaling in the CNS, with a focus on results from studies using genetic null mutants for LPA and S1P receptors. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.
Development of Our Current Understanding of Bioactive Lysophospholipids
Annals of the New York Academy of Sciences, 2006
Lysophosphatidic acid (LPA) serves as the prototypic lysophospholipid mediator that acts through G-protein-coupled receptors to evoke a host of responses in numerous target cells. The hormone-and growth-factor-like activities of LPA, mediated by distinct G proteins, were discovered about 10 years ago. Since then, considerable progress has been made in our understanding of LPA receptor signaling, culminating in the recent identification of a growing family of heptahelical receptors specific for LPA and the structurally related lysolipid, sphingosine-1-phosphate (S1P). In addition to stimulating G i-Rasmediated cell proliferation, LPA and S1P induce rapid G= 12/13-RhoAmediated cytoskeletal changes underlying such diverse responses as neurite retraction, cell rounding, and enhanced tumor cell invasiveness. LPA also triggers inhibition of gap-junctional communication. This overview focuses on how our understanding of LPA as an intercellular lipid mediator has developed during the last decade.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2004
Some of the biological effects of lipoproteins have been attributed to their association with lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), sphingosine-1-phosphate (S1P) and sphingosylphosphorylcholine (SPC). These lysophospholipids mediate multiple biological responses via several G protein-coupled receptors (GPR). The expression of these receptors, however, has not been systematically investigated in primary human monocytes and macrophages as major cells involved in atherosclerosis. The mRNAs for all 15 receptors described so far were detected in monocytes, macrophages, foam cells and high density lipoprotein (HDL 3)-treated cells using real time RT-PCR. Immunoblots revealed that S1P 1 , S1P 2 , S1P 4 , LPA 1 , LPA 2 and GPR65 are expressed in monocytes and macrophages, while S1P 5 and LPA 3 have not been detected. S1P 3 was induced during differentiation but down-regulated by lipid-loading and HDL 3 , whereas LPA 1 was down-regulated in differentiated macrophages. The influence of S1P on macrophages was investigated and the induction of CD32 indicates an enhanced phagocytic activity. Altogether, these data give insights into the expression and regulation of lysophospholipid receptors in primary human monocytes, macrophages and foam cells.
Bioactive Lysophospholipids and Their G Protein-Coupled Receptors
Experimental Cell Research, 1999
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are serum-borne lysophospholipids that signal through their cognate G protein-coupled receptors to evoke a great variety of responses in numerous cell types. In addition to stimulating cell proliferation and survival, LPA and S1P induce profound cytoskeletal changes through Rho-mediated signaling pathways, leading to such diverse responses as cell rounding, neurite retraction, and modulation of tumor cell invasiveness (transcellular migration). A major recent advance is the identification of a subfamily of heptahelical receptors for LPA and S1P.