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 eleven 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

See also

References
  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.
  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.
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