|Title||Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the Gi, Gq, and G12 families of heterotrimeric G proteins|
|Authors||Windh, R., Lee, M.J., Hla, T., An, S., Barr, A.J. and Manning, D.R.|
Sphingosine 1-phosphate (S1P) is one of several bioactive phospholipids that exert profound mitogenic and morphogenic actions. Originally characterized as a second messenger, S1P is now recognized to achieve many of its effects through cell surface, G protein-coupled receptors. We used a subunit-selective [35S]GTPγS binding assay to investigate whether the variety of actions exerted through Edg-1, a recently identified receptor for S1P, might be achieved through multiple G proteins. We found, employing both Sf9 and HEK293 cells, that Edg-1 activates only members of the Gi family, and not Gs, Gq, G12, or G13. We additionally established that Edg-1 activates Gi in response not only to S1P but also sphingosylphosphorylcholine; no effects of lysophosphatidic acid through Edg-1 were evident. Our assays further revealed a receptor(s) for S1P endogenous to HEK293 cells that mediates activation of G13 as well as Gi. Because several of the biological actions of S1P are assumed to proceed through the G12/13 family, we tested whether Edg-3 and H218/Edg-5, two other receptors for S1P, might have a broader coupling profile than Edg-1. Indeed, Edg-3 and H218/Edg-5 communicate not only with Gi but also with Gq and G13. These studies represent the first characterization of S1P receptor activity through G proteins directly and establish fundamental differences in coupling.
|Journal||Journal of Biological Chemistry|
|Journal citation||274 (39), pp. 27351-27358|
|Publisher||American Society for Biochemistry and Molecular Biology|
|Digital Object Identifier (DOI)||https://doi.org/10.1074/jbc.274.39.27351|
|Published||24 Sep 1999|