GPR35 is a novel lysophosphatidic acid receptor

GPR35 is a novel lysophosphatidic acid receptor
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DOI:
10.1016/j.bbrc.2010.03.169
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发表时间:
2010-04-30
影响因子:
3.1
通讯作者:
Sugiura, Takayuki
Sugiura, Takayuki
中科院分区:
生物学4区
文献类型:
--
作者:
Oka, Saori;Ota, Ryo;Sugiura, Takayuki

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GPR 35是1998年鉴定的视紫红质样G蛋白偶联受体。据报道,犬尿烯酸,色氨酸代谢物,可以作为GPR 35的内源性配体。然而,引发细胞反应所需的犬尿烯酸浓度通常很高,这增加了可能存在另一种内源性配体的可能性。在这项研究中,我们寻找GPR 35的另一种内源性配体。最后,我们发现,2-酰基溶血磷脂酸诱导的GPR 35表达的HEK 293细胞中的Ca 2+反应的幅度显着大于在载体转染的对照细胞。在1-酰基溶血磷脂酸的情况下,这种差异不明显。2-酰基溶血磷脂酸还引起RhoA的持续激活和细胞外信号调节激酶的磷酸化,并触发GPR 35分子的内化。这些结果强烈表明,2-酰基溶血磷脂酸是GPR 35的内源性配体。(C)2010年爱思唯尔公司All rights reserved.
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 Ca2+ 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. (C) 2010 Elsevier Inc. All rights reserved.