Identification and Characterization of a Novel Lysophosphatidic Acid Receptor, p2y5/LPA6
Identification and Characterization of a Novel Lysophosphatidic Acid Receptor, p2y5/LPA6
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DOI：
10.1074/jbc.m808506200
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发表时间：
2009-06-26
影响因子：
4.8
通讯作者：
Ishii, Satoshi
中科院分区：
文献类型：
--
作者：
Yanagida, Keisuke;Masago, Kayo;Ishii, Satoshi
p2 y 5是一种孤儿G蛋白偶联受体，与第四种溶血磷脂酸（LPA）受体LPA密切相关（4）。在这里，我们报告，p2 y 5是一个新的LPA受体耦合到G（13）-Rho信号通路。外源性表达p2 y 5的“LPA受体缺失”RH 7777和B103细胞显示[H-3] LPA结合、LPA诱导的[S-35]鸟苷5 '-3-O-（硫代）三磷酸结合、Rho依赖性细胞形态改变和G（s/13）嵌合蛋白介导的cAMP积累。LPA诱导的人脐静脉内皮细胞收缩被小干扰RNA敲低内源性表达的p2 y 5抑制。我们还发现2-酰基-LPA比1-酰基-LPA对p2 y 5具有更高的活性。最近的一项研究表明，p2 y 5是人类毛发生长所必需的LPA受体。我们证实p2 y 5是一种功能性LPA受体，并建议将该受体命名为LPA（6）。
p2y5 is an orphan G protein-coupled receptor that is closely related to the fourth lysophosphatidic acid (LPA) receptor, LPA(4). Here we report that p2y5 is a novel LPA receptor coupling to the G(13)-Rho signaling pathway. "LPA receptor-null" RH7777 and B103 cells exogenously expressing p2y5 showed [H-3] LPA binding, LPA-induced [S-35] guanosine 5'-3-O-(thio) triphosphate binding, Rho-dependent alternation of cellular morphology, and G(s/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 LPA(6).