GPR34 is a receptor for lysophosphatidylserine with a fatty acid at the sn-2 position
GPR34 is a receptor for lysophosphatidylserine with a fatty acid at the sn-2 position
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DOI：
10.1093/jb/mvs011
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发表时间：
2012-05-01
影响因子：
2.7
通讯作者：
Aoki, Junken
中科院分区：
文献类型：
--
作者：
Kitamura, Hajime;Makide, Kumiko;Aoki, Junken
GPR34是一种G蛋白偶联受体，属于P2Y家族。在这里，我们试图解决关于它是否是一个功能性溶血磷脂酰丝氨酸(LysoPS)受体的相互矛盾的报道。在表达人、小鼠或大鼠GPR34和Gαq和Gαi1之间嵌合体(Gq/i1)的HEK293细胞中，LysoPS迅速升高细胞内钙离子水平([Ca2+](I))。LysoPS还刺激表达GPR34的HEK293细胞释放碱性磷酸酶(AP)标记的转化生长因子α(AP-TGFα)，并诱导表达GPR34的CHO-K1细胞迁移。其他溶血磷脂不能诱导这些作用。LYSOPS丝氨酸残基的取代取消了LYSOPS与GPR34的反应性，表明GPR34严格识别LYSOPS的丝氨酸头基。重组磷脂酰丝氨酸特异性磷脂酶A(1)可使PS的sn-1位脂肪酸去酰化并产生2-酰基-LysoPS，但不能催化失活突变体PS(1)刺激表达GPR34的细胞释放AP-转化生长因子α。与结果一致的是，在野生型PS-PLA(1)处理的细胞中检测到LysoPS，而在突变型PS-PLA(1)处理的细胞中未检测到LysoPS。用聚乳酸(1)处理的PS比用聚乳酸(2)处理的PS更有效地刺激AP-TGFα的释放。此外，抗迁移的2-酰基-1-脱氧-LysoPS是一个2-酰基-2-脱氧-LysoPS类似物，比1-酰基-2-脱氧-LysoPS更有效。目前的研究证实，GPR34是LysoPS的细胞受体，特别是sn-2位的脂肪酸。
GPR34 is a G protein-coupled receptor belonging to the P2Y family. Here, we attempted to resolve conflicting reports about whether it is a functional lysophosphatidylserine (LysoPS) receptor. In HEK293 cells expressing human, mouse or rat GPR34 and G alpha chimera between G alpha q and G alpha i1(Gq/i1), LysoPS quickly elevated intracellular Ca2+ ion levels ([Ca2+](i)). LysoPS also stimulated alkaline phosphatase (AP)-tagged TGF alpha (AP-TGF alpha) release in GPR34-expressing HEK293 cells and induced the migration of CHO-K1 cells expressing GPR34. Other lysophospholipids did not induce these actions. Replacement of the serine residue of LysoPS abolished the reactivity of LysoPS with GPR34, indicating that GPR34 strictly recognizes the serine head group of LysoPS. Recombinant phosphatidylserine-specific phospholipase A(1) (PS-PLA(1)) that deacylates fatty acid at the sn-1 position of PS and produces 2-acyl-LysoPS, but not catalytically inactive mutant PS-PLA(1), stimulated the release of AP-TGF alpha from GPR34-expressing cells. Consistent with the result, LysoPS was detected in the cells treated with wild-type PS-PLA(1) but not with the mutant PS-PLA(1). PS treated with PLA(1) was much more effective at stimulating AP-TGF alpha release than PS treated with PLA(2). In addition, migration-resistant 2-acyl-1-deoxy-LysoPS, a 2-acyl-LysoPS analogue, was much more potent than 1-acyl-2-deoxy-LysoPS. The present studies confirm that GPR34 is a cellular receptor for LysoPS, especially with a fatty acid at the sn-2 position.