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.
Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1
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C. M. Gerben ZONDAG, R. Friso POSTMA, Ingrid VAN ETTEN, Ingrid VERLAAN, H. Wouter MOOLENAAR; Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1. Biochem J 1 March 1998; 330 (2): 605–609. doi: https://doi.org/10.1042/bj3300605
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