Identification and characterization of a novel lysophosphatidic acid receptor, p2y5/LPA6.
p2y5 is an orphan G protein-coupled receptor that is closely related to the fourth lysophosphatidic acid (LPA) receptor, LPA4. Here we report that p2y5 is a novel LPA receptor coupling to the G13-Rho signaling pathway. "LPA receptor-null" RH7777 and B103 cells exogenously expressing p2y5 showed [3H]LPA binding, LPA-induced [35S]guanosine 5'-3-O-(thio)triphosphate binding, Rho-dependent alternation of cellular morphology, and Gs/13 chimeric protein-mediated cAMP accumulation. LPA-induced contraction of human umbilical vein endothelial cells was suppressed by small interfering RNA knockdown of endogenously expressed p2y5. We also found that 2-acyl-LPA had higher activity to p2y5 than 1-acyl-LPA. A recent study has suggested that p2y5 is an LPA receptor essential for human hair growth. We confirmed that p2y5 is a functional LPA receptor and propose to designate this receptor LPA6.
Yanagida
Keisuke
K
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Univerfsity of Tokyo, Tokyo, Japan.
Masago
Kayo
K
Nakanishi
Hiroki
H
Kihara
Yasuyuki
Y
Hamano
Fumie
F
Tajima
Yoko
Y
Taguchi
Ryo
R
Shimizu
Takao
T
Ishii
Satoshi
S
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D008246:Lysophospholipids / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D011869:Radioligand Assay; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid
D002118:Calcium; D000242:Cyclic AMP; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008246:Lysophospholipids; D018048:Receptors, Purinergic P2; C082320:LPAR4 protein, human; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid