Identification and Characterization of a Novel Lysophosphatidic Acid Receptor, p2y5/LPA6 |
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| Authors: | Keisuke Yanagida Kayo Masago Hiroki Nakanishi Yasuyuki Kihara Fumie Hamano Yoko Tajima Ryo Taguchi Takao Shimizu and Satoshi Ishii |
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| Institution: | From the Departments of ‡Biochemistry and Molecular Biology and ;§Metabolome, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 and ;¶CREST and ;‖PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-8613, Japan |
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| Abstract: | 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. |
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