Lysophospholipid receptor

The lysophospholipid receptor (LPL-R) group are members of the G protein-coupled receptor family of integral membrane proteins that are important for lipid signaling.^[1] In humans, there are eight LPL receptors, each encoded by a separate gene. These LPL receptor genes are also sometimes referred to as "Edg” (an acronym for endothelial differentiation gene).

Ligands

The ligands for LPL-R group are the lysophospholipid extracellular signaling molecules, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P).

Origin of name

The term lysophospholipid (LPL) refers to any phospholipid that is missing one of its two O-acyl chains. Thus, LPLs have a free alcohol in either the sn-1 or the sn-2 position. The prefix 'lyso-' comes from the fact that lysophospholipids were originally found to be hemolytic, however it is now used to refer generally to phospholipids missing an acyl chain. LPLs are usually the result of phospholipase A-type enzymatic activity on regular phospholipids such as phosphatidylcholine or phosphatidic acid, although they can also be generated by the acylation of glycerophospholipids or the phosphorylation of monoacylglycerols. Some LPLs serve important signaling functions such as lysophosphatidic acid.

Function

LPL receptor ligands bind to and activate their cognate receptors located in the cell membrane. Depending on which ligand, receptor, and cell type is involved, the activated receptor can have a range of effects on the cell. These include primary effects of inhibition of adenylyl cyclase and release of calcium from the endoplasmic reticulum, as well as secondary effects of preventing apoptosis and increasing cell proliferation.^[2]

Group members

The following is a list of the eleven known human LPL receptors:^[1]^[3]^[4]

Gene Symbol	IUPHAR Symbol	Gene / Protein Name	Agonist Ligand	Synonyms
LPAR1	272	lysophosphatidic acid receptor 1	LPA	EDG2
LPAR2	273	lysophosphatidic acid receptor 2	"	EDG4
LPAR3	274	lysophosphatidic acid receptor 3	"	EDG7
LPAR4	LPA₄	lysophosphatidic acid receptor 4	"	GPR23
LPAR5	LPA₅	lysophosphatidic acid receptor 5	"	GPR92
LPAR6	LPA₆	lysophosphatidic acid receptor 6	"	P2RY5
S1PR1	275	sphingosine-1-phosphate receptor 1	S1P	EDG1
S1PR2	276	sphingosine-1-phosphate receptor 2	"	EDG5
S1PR3	277	sphingosine-1-phosphate receptor 3	"	EDG3
S1PR4	278	sphingosine-1-phosphate receptor 4	"	EDG6
S1PR5	279	sphingosine-1-phosphate receptor 5	"	EDG8

References

↑ 1.0 1.1 Chun J, Goetzl EJ, Hla T, Igarashi Y, Lynch KR, Moolenaar W, Pyne S, Tigyi G (2002). "International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature". Pharmacol Rev 54 (2): 265–9. doi:10.1124/pr.54.2.265. PMID 12037142.
↑ Meyer zu Heringdorf D, Jakobs KH (2007). "Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism". Biochim Biophys Acta 1768 (4): 923–40. doi:10.1016/j.bbamem.2006.09.026. PMID 17078925.
↑ Choi JW, Herr DR, Noguchi K, Yung YC, Lee C-W, Mutoh T, Lin M-E, Teo ST, Park KE, Mosley AN, Chun J (January 2010). "LPA Receptors: Subtypes and Biological Actions". Annual Review of Pharmacology and Toxicology 50 (1): 157–186. doi:10.1146/annurev.pharmtox.010909.105753. PMID 20055701.
↑ Pasternack SM, von Kügelgen I, Aboud KA, Lee YA, Rüschendorf F, Voss K, Hillmer AM, Molderings GJ, Franz T, Ramirez A, Nürnberg P, Nöthen MM, Betz RC (March 2008). "G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth". Nat. Genet. 40 (3): 329–34. doi:10.1038/ng.84. PMID 18297070.

External links

"Lysophospholipid Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Lysophospholipid receptors at the US National Library of Medicine Medical Subject Headings (MeSH)

Membrane proteins, receptors: cell surface receptors

G protein-coupled receptor

Class A	Eicosanoid receptor (Prostaglandin receptor) Protease-activated receptor Neurotransmitter receptor Purinergic receptor Biogenic amine receptor Olfactory receptor

Class B	Secretin receptor

Class C	Metabotropic glutamate receptor

Class D	Pheromone receptor

Class E	cAMP receptor

Class F	Frizzled/smoothened

Ligand-gated ion channel

Purinergic receptor

Enzyme-linked receptor

Other/ungrouped

See also: cell surface receptor deficiencies

Index of signal transduction

Description	Intercellular neuropeptides growth factors cytokines hormones Cell surface receptors ligand-gated enzyme-linked G protein-coupled immunoglobulin superfamily integrins neuropeptide growth factor cytokine Intracellular adaptor proteins GTP-binding MAP kinase Calcium signaling Lipid signaling Pathways hedgehog Wnt TGF beta MAPK ERK notch JAK-STAT apoptosis hippo TLR

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Adhesion	ADGRG (1 2 3 4 5 6 7)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

Index of signal transduction

Description	Intercellular neuropeptides growth factors cytokines hormones Cell surface receptors ligand-gated enzyme-linked G protein-coupled immunoglobulin superfamily integrins neuropeptide growth factor cytokine Intracellular adaptor proteins GTP-binding MAP kinase Calcium signaling Lipid signaling Pathways hedgehog Wnt TGF beta MAPK ERK notch JAK-STAT apoptosis hippo TLR

Cell signaling: lipid signaling

Intracellular

Cell membrane	PIP₂ DAG

Gq alpha subunit	Phosphoinositide phospholipase C

Cytosol	Phospholipase Phospholipase A2 Phospholipase C Phospholipase D IP₃

Sarcoplasmic reticulum	IP₃ receptor

Other	Protein kinase B Diacylglycerol Protein kinase C

Extracellular lipid ligands

receptor: Lysophospholipid receptor
S1PR1

Index of signal transduction

Description	Intercellular neuropeptides growth factors cytokines hormones Cell surface receptors ligand-gated enzyme-linked G protein-coupled immunoglobulin superfamily integrins neuropeptide growth factor cytokine Intracellular adaptor proteins GTP-binding MAP kinase Calcium signaling Lipid signaling Pathways hedgehog Wnt TGF beta MAPK ERK notch JAK-STAT apoptosis hippo TLR