Type of G protein-coupled 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).

## Contents

* 1 Ligands
* 2 Origin of name
* 3 Function
* 4 Group members
* 5 See also
* 6 References
* 7 External links

## Ligands[edit]

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

## Origin of name[edit]

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[edit]

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[edit]

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

## See also[edit]

* Lipid signaling
* Gintonin

## References[edit]

1. ^ a b 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.
2. ^ 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.
3. ^ Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, Lin ME, 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.
4. ^ 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[edit]

* "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)

* v
* t
* e

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|

* Serine/threonine-specific protein kinase
* Receptor tyrosine kinase
* Guanylate cyclase

Other/ungrouped|

* Asialoglycoprotein receptor
* Tumor necrosis factor receptor
* Immunoglobulin superfamily
* N-Acetylglucosamine receptor
* Neuropilins
* Transferrin receptor
* EDAR
* Lipoprotein receptor-related protein
* Progestin and adipoQ receptor

* v
* t
* e

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
* GHB receptor
* Histamine
* H1
* H2
* H3
* H4
* Melatonin (1A
* 1B
* 1C)
* TAAR (1
* 2
* 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)
* Hydroxycarboxylic acids
* 1
* 2
* 3
* Lysophosphatidic acid (1
* 2
* 3
* 4
* 5
* 6)
* Lysophospholipid (1
* 2
* 3
* 4
* 5
* 6
* 7
* 8)
* 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 (1
* 2))
* 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)
* 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|

| Taste, bitter|

* 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
* Vomeronasal receptor type 1

|

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
* 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

| Adhesion|

* ADGRG (1
* 2
* 3
* 4
* 5
* 6
* 7)

|

Orphan|

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

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, sweet|

* TAS1R
* 1
* 2
* 3
* Vomeronasal receptor, type 2

|

Other|

* Calcium-sensing receptor
* GABAB (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

* v
* t
* e

Cell signaling: lipid signaling

Extracellular|

| Eicosanoids|

* Classic: Eoxins;
* Leukotrienes (LTR)
* Prostacyclin (IPR)
* Prostaglandins (PGR)
* Thromboxane (TXR)
* Nonclassic: EETs
* Endocannabinoids (CBR)
* Epi-lipoxins (FPR2)
* Hepoxilins
* Isoprostanes
* Lipoxins (FPR2)
* Oxoeicosanoids (OXER)
* Resolvins (FPR2)

|

Lysophospholipids|

* LPA (LPAR)
* S1P (S1PR)

Steroids|

* Bile acids (GPBAR)
* Neurosteroids
* Pheromones (VNR)

Others|

* PAF (PAFR)
* Retinal (RHO)

Intracellular|

| Nuclear receptor|

* Steroids: Sex steroids: Androgens (AR)
* Estrogens (ER)
* Progestogens (PR); Corticosteroids: Glucocorticoids (GR)
* Mineralocorticoids (MR); Others: Bile acids (FXR)
* Calcitriol (VDR); Others: Eicosanoids (PPAR)
* Free fatty acids (PPAR)
* Retinoic acid (RAR, RXR)

|

Second messenger|

* General: Arachidonic acid
* DAG (PKC, TRPC)
* IP3 (IP3R, RyR)
* Phosphatidic acid
* Phosphoinositides: PIP2 (IRKs)
* PIP3 (PKB/Akt, Btk, PDPK1)
* PtdIns(3,4)P2 (PKB/Akt, PDPK1); Sphingolipids: C1P
* Ceramide (CAPPs, KSR1, PKCζ, CTSD)
* Glucosylceramides
* S1P
* Sphingosine (SDK1, PKH, YPK)

Precursors|

| General|

* Fatty acids (ω-3, ω-6)

|

Steroids|

* Squalene
* Lanosterol
* Cholesterol

* v
* t
* e

Lysophospholipid signaling modulators

Receptor
(ligands)|

| LPAR|

* Agonists: 1-Oleoyl-LPA
* 1-Palmitoyl-LPA
* GRI-977143
* LPA
* OMPT

* Antagonists: H2L-5186303
* H2L-5765834
* Ki-16425
* TC-LPA5 4
* VPC-32183

|

S1PR|

* Agonists: Amiselimod
* Cenerimod
* Ceralifimod
* CS-2100
* CYM-5442
* CYM-5520
* CYM 5541
* CYM-50260
* CYM-50308
* Dihydro-S1P (sphinganine 1-phosphate)
* Fingolimod
* Fingolimod phosphate
* KRP-203
* Mocravimod
* Phyto-S1P
* Ponesimod
* RP-001
* RP-002
* RPC-1063
* SEW-2871
* Siponimod
* S1P
* SPC
* TC-G 1006
* TC-SP 14
* W-061
* XAX-162

* Antagonists: CS-0777
* CYM-50358
* JTE-013
* TY-52156
* VPC-23019
* W-146

* Unsorted: Etrasimod

Enzyme
(inhibitors)|

| SPT|

* Myriocin

|

Ceramidase|

* Ceranib 1
* OEA

SphK|

* N,N-DMS
* Safingol
* SKI II

Others|

* Precursors: LPA: LPC; S1P: Palmitoyl-CoA
* Serine
* 3-Ketosphinganine (dehydrosphingosine)
* Dihydrosphingosine (sphinganine)
* Dihydroceramide
* Ceramide
* Sphingosine

See also: Receptor/signaling modulators
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[LPAR]: Lysophosphatidic acid receptor
*[S1PR]: Sphingosine-1-phosphate receptor
*[SPT]: Serine C-palmitoyltransferase
*[SphK]: Sphingosine kinase