Lee M J, Thangada S, Liu C H, Thompson B D, Hla T
Department of Physiology, University of Connecticut School of Medicine, Farmington, Connecticut 06030, USA.
J Biol Chem. 1998 Aug 21;273(34):22105-12. doi: 10.1074/jbc.273.34.22105.
EDG-1, an inducible G-protein-coupled receptor from vascular endothelial cells, is a high affinity receptor for sphingosine 1-phosphate (SPP) (Lee, M-J., van Brocklyn, J. R., Thangada, S., Liu, C. H., Hand, A. R., Menzeleev, R., Spiegel, S., and Hla, T. (1998) Science 279, 1552-1555). In this study, we show that lysophosphatidic acid (LPA), a platelet-derived bioactive lipid structurally related to SPP, is an agonist for EDG-1. LPA binds to EDG-1 receptor with an apparent Kd of 2.3 microM. In addition, LPA binding to EDG-1 induces receptor phosphorylation, mitogen-activated protein kinase activation, as well as Rho-dependent morphogenesis and P-cadherin expression. These data suggest that LPA is a low-affinity agonist for EDG-1. Activation of the endothelial receptor EDG-1 by platelet-derived lipids LPA and SPP may be important in thrombosis and angiogenesis, conditions in which critical platelet-endothelial interactions occur.
EDG-1是一种来自血管内皮细胞的可诱导型G蛋白偶联受体，是1-磷酸鞘氨醇（SPP）的高亲和力受体（李，M-J.，范·布罗克林，J.R.，坦加达，S.，刘，C.H.，汉德，A.R.，门泽列夫，R.，施皮格尔，S.，和赫拉，T.（1998年）《科学》279卷，第1552 - 1555页）。在本研究中，我们发现溶血磷脂酸（LPA），一种在结构上与SPP相关的血小板衍生生物活性脂质，是EDG-1的激动剂。LPA以2.3微摩尔的表观解离常数（Kd）与EDG-1受体结合。此外，LPA与EDG-受体的结合诱导受体磷酸化、丝裂原活化蛋白激酶激活，以及Rho依赖性形态发生和P-钙黏蛋白表达。这些数据表明LPA是EDG-1的低亲和力激动剂。血小板衍生脂质LPA和SPP对内皮受体EDG-1的激活在血栓形成和血管生成中可能很重要，在这些情况下会发生关键的血小板 - 内皮相互作用。
