Novel clusters of receptors for sphingosine-1 phosphate, sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: New receptors for "old" ligands
Novel clusters of receptors for sphingosine-1 phosphate, sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: New receptors for "old" ligands
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DOI：
10.1002/jcb.20092
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发表时间：
2004-08-01
影响因子：
4
通讯作者：
Kostenis, E
中科院分区：
文献类型：
--
作者：
Kostenis, E
（溶索）磷脂介质鞘氨醇-1-磷酸（S1P）、溶血磷脂酸（LPA）、鞘氨酰胆碱（SPC）和磷脂酸（PA）调节多种细胞反应，如增殖、存活和死亡、细胞骨架重排、细胞运动和分化等。信号是复杂的，许多信号事件是通过激活细胞表面7跨膜（7TM） G蛋白偶联受体介导的。目前已鉴定出5个高亲和力的S1P受体，命名为S1P(1,2,3,4,5)（以前称为内皮分化基因（edg） 1,5,3,6,8）。最近，孤儿受体GPR63被鉴定为低亲和力的S1P受体，在结构上远离S1P（1-5）家族。孤儿gpr3,6,12簇，在系统发育上与edg和黑素皮质素受体相关，似乎受到S1P和SPC的调节，尽管这三种受体都是气体腺苷酸环化酶（AC）途径的强组成刺激物，不需要额外的配体刺激，而是相反的激动作用来控制活性。卵巢癌G蛋白偶联受体I （OGR1）和GPR4是两个结构密切相关的受体，在功能和结合研究中被指定为SPC的高亲和力分子靶点。然而，最近，OGR1和GPR4都被描述为具有响应质子向细胞发出信号能力的受体。LPA通过激活G蛋白偶联LPA（1-3）受体（以前称为edg2, 4,7）来发挥其生物学作用。第四个高亲和力LPA受体已被确定：P2Y9 （GPR23）在结构上与核苷酸受体相关，系统发育上与高亲和力LPA（1-3）簇相当遥远。本文综述了现有的溶磷脂受体家族，以及它们作为高亲和力或低亲和力配体将细胞外信号传递到细胞内反应的脂质激动剂的谱。最近去孤儿脂受体，内外已知的脂受体簇将受到特别的关注。(C) 2004 Wiley-Liss, Inc。
The (lyso)phospholipid mediators sphingosine-1-phosphate (S1P), lysophosphatidic acid (LPA), sphingosylphosphorylcholine (SPC), and phosphatidic acid (PA) regulate diverse cellular responses such as proliferation, survival and death, cytoskeletal rearrangements, cell motility, and differentiation among many others. Signaling is complex and many signaling events are mediated through the activation of cell surface seven transmembrane (7TM) G protein coupled receptors. Five high affinity receptors for S1P have been identified so far and named S1P(1,2,3,4,5) (formerly referred to as endothelial differentiation gene (edg)1, 5, 3, 6, 8). Recently, the orphan receptor GPR63 was identified a low affinity S1P receptor structurally distant from the S1P(1-5) family. The orphan GPR3, 6, 12 cluster, phylogenetically related to the edg and melanocortin receptors appears to be subject to modulation by S1P and SPC although all three receptors are strong constitutive stimulators of the Gas-adenylyl cyclase (AC) pathway and would not require additional ligand stimulation but rather inverse agonism to control activity. Ovarian cancer G protein coupled receptor I (OGR1) and GPR4, two structurally closely related receptors were assigned in functional and binding studies as high affinity molecular targets for SPC. Very recently, however, both OGR1 and GPR4 were described as receptors endowed with the ability to signal cells in response to protons. LPA exerts its biological effects through the activation of G protein Coupled LPA(1-3) receptors (formerly referred to as edg2, 4, 7). A fourth high affinity LPA receptor has been identified: P2Y9 (GPR23) structurally related to nucleotide receptors and phylogenetically quite distant from the high affinity LPA(1-3) cluster. This review attempts to give an overview about the existing families of lysophosholipid receptors and the spectrum of lipid agonists they use as high or low affinity ligands to relay extracellular signals into intracellular responses. Recently deorphaned lipid receptors, within and outside the known lipid receptor clusters will receive particular attention. (C) 2004 Wiley-Liss, Inc.