Identification and Characterization of a Novel Lysophosphatidic Acid Receptor, p2y5/LPA6

K Yanagida, K Masago, H Nakanishi, Y Kihara, F Hamano, Y Tajima, R Taguchi, T Shimizu and S. Ishii

The Journal of Biological Chemistry, 2009, 284(26), 17731-17741. DOI: 10.1074/jbc.M808506200


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.

ASCI-ID: 188-5373