Regulation of mammalian physiology, development, and disease by the sphingosine 1-phosphate and lysophosphatidic acid receptors.

Regulation of mammalian physiology, development, and disease by the sphingosine 1-phosphate and lysophosphatidic acid receptors.
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DOI:
10.1021/cr200273u
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发表时间:
2011-10-12
期刊:
影响因子:
62.1
通讯作者:
Hla, Timothy
Hla, Timothy
中科院分区:
化学1区
文献类型:
--
作者:
Blaho, Victoria A.;Hla, Timothy

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溶血磷脂这个绰号包含了两大类膜衍生脂质:甘油磷脂和鞘脂。1这两个分支的主要代表是溶血磷脂酸(LPA)和1-磷酸鞘氨醇(S1 P),其大部分活性通过对LPA或S1 P具有高度特异性的多个G蛋白偶联受体介导。2,3与S1 P不同,S1 P是单一分子物种(2S-氨基-1-(磷酸二氢盐)-4E-十八烯-1,3R-二醇),LPA(1-O-酰基-2-羟基-sn-甘油-3-磷酸)实际上是一组不同的分子,(例如,16:0、18:0)或不饱和(例如,16:1、18:1、18:2、20:4)脂肪酸链在甘油主链的sn-1或sn-2位酯化。4,5这也可以在sn-1位被修饰为烷基或烯基。6 LP家族的其他生物活性成员包括LPA类似物环磷脂酸(cPA)、鞘氨醇磷脂酰胆碱(SPC)、溶血磷脂酰胆碱(LPC)、溶血磷脂酰丝氨酸(LPS)和溶血磷脂酰肌醇(LPI)。1,5,7许多新出现的报告表明,在哺乳动物生物学的其他作用,不太好的特点LP成员,以及。8在过去的十年中,我们对LP生物学的理解呈指数级增长,这得益于LP受体的鉴定,LPA和S1 P受体敲除小鼠的产生和分析,以及作为受体特异性激动剂或拮抗剂的小分子化合物。三、九、十
The moniker lysophospholipid incorporates two broad families of membrane-derived lipids: the glycerophospholipids and the sphingolipids. 1 Primary representatives of these two arms are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), the majority of whose activities are mediated via multiple G-protein-coupled receptors with a high degree of specificity for either LPA or S1P. 2, 3 Unlike S1P, which is a single molecular species (2S-amino-1-(dihydrogen phosphate)-4E-octadecene-1, 3R-diol), LPA (1-O-acyl-2-hydroxy-sn-glycero-3-phosphate) is actually a diverse group of molecules consisting of either a saturated (eg, 16: 0, 18: 0) or unsaturated (eg, 16: 1, 18: 1, 18: 2, 20: 4) fatty acid chain esterified at the sn-1 or sn-2 position of a glycerol backbone. 4, 5 This can also be modified to alkyl or alkenyl at the sn-1 position. 6 Other bioactive members of the LP family include the LPA analogues cyclic phosphatidic acid (cPA), sphigosylphosphotidylcholine (SPC), lysophosphatidylcholine (LPC), lysophosphatidylserine (LPS), and lysophosphatidylinositol (LPI). 1, 5, 7 Numerous emerging reports indicate roles in mammalian biology for other, less well-characterized LP members, as well. 8 In the past decade, our understanding of LP biology has expanded exponentially, fueled by the identification of LP receptors, generation and analysis of LPA-and S1P-receptor knockout mice, and small molecule compounds functioning as receptor-specific agonists or antagonists. 3, 9, 10
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