title: GPR35 is a novel lysophosphatidic acid receptor.
abstract: GPR35 is a rhodopsin-like G protein-coupled receptor identified in 1998. It has been reported that kynurenic acid, a tryptophan metabolite, may act as an endogenous ligand for GPR35. However, the concentrations of kynurenic acid required to elicit the cellular responses are usually high, raising the possibility that another endogenous ligand may exist. In this study, we searched for another endogenous ligand for GPR35. Finally, we found that the magnitude of the Ca(2+) response induced by 2-acyl lysophosphatidic acid in the GPR35-expressing HEK293 cells was markedly greater than that in the vector-transfected control cells. Such a difference was not apparent in the case of 1-acyl lysophosphatidic acid. 2-Acyl lysophosphatidic acid also caused the sustained activation of RhoA and the phosphorylation of extracellular signal-regulated kinase, and triggered the internalization of the GPR35 molecule. These results strongly suggest that 2-acyl lysophosphatidic acid is an endogenous ligand for GPR35.
authors.affiliation: Teikyo University, Sagamihara, Kanagawa 252-5195, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Oka
authors.forename: Ryo
authors.initials: R
authors.lastname: Ota
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Shima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamashita
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sugiura
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D063386:Cannabinoid Receptor Agonists; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007736:Kynurenic Acid / Q000494:pharmacology; D008024:Ligands; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D043882:Receptors, Cannabinoid / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D063386:Cannabinoid Receptor Agonists; C111379:GPR35 protein, human; D008024:Ligands; D008246:Lysophospholipids; D011688:Purinones; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; C066737:RHOA protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D020742:rhoA GTP-Binding Protein; C011145:zaprinast; D007736:Kynurenic Acid; D000241:Adenosine; C032881:lysophosphatidic acid; D002118:Calcium