Zondag G C, Postma F R, Etten I V, Verlaan I, Moolenaar W H
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Biochem J. 1998 Mar 1;330 ( Pt 2)(Pt 2):605-9. doi: 10.1042/bj3300605.
Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are structurally related lipid mediators that act on distinct G-protein-coupled receptors to evoke similar responses, including Ca2+ mobilization, adenylate cyclase inhibition, and mitogen-activated protein (MAP) kinase activation. However, little is still known about the respective receptors. A recently cloned putative LPA receptor (Vzg-1/Edg-2) is similar to an orphan Gi-coupled receptor termed Edg-1. Here we show that expression of Edg-1 in Sf9 and COS-7 cells results in inhibition of adenylate cyclase and activation of MAP kinase (Gi-mediated), but not Ca2+ mobilization, in response to S1P. These responses are specific in that (i) S1P action is not mimicked by LPA, and (ii) Vzg-1/Edg-2 cannot substitute for Edg-1. Thus the Edg-1 receptor is capable of mediating a subset of the cellular responses to S1P.
鞘氨醇-1-磷酸(S1P)和溶血磷脂酸(LPA)是结构相关的脂质介质,它们作用于不同的G蛋白偶联受体以引发相似的反应,包括钙离子动员、腺苷酸环化酶抑制以及丝裂原活化蛋白(MAP)激酶激活。然而,关于各自的受体仍知之甚少。最近克隆的一个假定的LPA受体(Vzg-1/Edg-2)与一个名为Edg-1的孤儿Gi偶联受体相似。在此我们表明,Edg-1在Sf9和COS-7细胞中的表达导致腺苷酸环化酶受到抑制以及MAP激酶激活(Gi介导),但对S1P无钙离子动员反应。这些反应具有特异性,因为(i)LPA不能模拟S1P的作用,且(ii)Vzg-1/Edg-2不能替代Edg-1。因此,Edg-1受体能够介导细胞对S1P的一部分反应。