Disease relevance of Edg1

• The novel sphingosine 1-phosphate receptor AGR16 is coupled via pertussis toxin-sensitive and -insensitive G-proteins to multiple signalling pathways [1].
• In this paper, we report that in PC12 cells and dorsal root ganglion neurons, NGF translocates SphK1 to the plasma membrane and differentially activates the S1P receptors S1P1 and S1P2 in a SphK1-dependent manner, as determined with specific inhibitors and small interfering RNA targeted to SphK1 [2].
• Of five S1P receptor subtypes, Edg-1 and Edg-5 are expressed in the glioma cells, as evidenced by Northern blotting [3].

High impact information on Edg1

• Conversely, when overexpressed in PC12 cells, transactivation of S1P1 by NGF markedly enhanced neurite extension and stimulation of the small GTPase Rac, important for the cytoskeletal changes required for neurite extension [2].
• NGF-induced neurite extension was suppressed by down-regulation of S1P1 expression with antisense RNA [2].
• Identification of Edg1 receptor residues that recognize sphingosine 1-phosphate [4].
• Originating from its DNA sequence, a computational model of the Edg1 receptor has been developed that predicts critical interactions with its ligand, sphingosine 1-phosphate [4].
• A similar but less dramatic effect was observed in cells overexpressing Edg-3 but not with Edg-1 [5].

Chemical compound and disease context of Edg1

• Differential roles of Edg-1 and Edg-5, sphingosine 1-phosphate receptors, in the signaling pathways in C6 glioma cells [3].

Biological context of Edg1

• Analogue 26 (S1P1 IC50 = 0.6 nM) has an excellent pharmacokinetics profile in the rat and dog and is efficacious in a rat skin transplant model, indicating that S1P3 receptor agonism is not a component of immunosuppressive efficacy [6].
• The genes that we have identified, including MKP3, a regulator of ERK signaling, and the sphingosine-1-phosphate receptor edg3/lp(B3), may play important roles in mediating Schwann cell differentiation [7].
• Role of the sphingosine 1-phosphate receptor EDG-1 in vascular smooth muscle cell proliferation and migration [8].

Anatomical context of Edg1

• Sequence analysis of this clone reveals the structural features characteristic of this superfamily, with a high degree of sequence similarity to the Edg-1 receptor previously reported to be expressed in vascular endothelial cells [9].
• In the present investigation of rat thyroid FRTL-5 cells, we show using reverse-transcriptase PCR that these cells express both Edg-1 and Edg-5 [10].
• Sphingosine-1-phosphate and the leading Edg-1 of vascular smooth muscle cells [11].

Associations of Edg1 with chemical compounds

• Supporting this idea, mRNAs of recently identified S1P specific receptors, Edg-1 and AGR16/H218, were expressed in C6 cells [12].
• Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3 [6].
• We show using a [35S]GTPgammaS-binding assay that sphingosylphosphorylcholine (SPC), which binds to both Edg-1 and EDG-5, activates Gq, Gi-2, and Gi-3 proteins [10].
• These results suggest that functional receptors like lysophospholipid receptor Edg-1, which can inhibit adenylate cyclase via Gi protein, are lacking in the rat heart [13].
• Change from cyclosporine to combination therapy of mycophenolic acid with the new sphingosine-1-phosphate receptor agonist, KRP-203, prevents host nephrotoxicity and transplant vasculopathy in rats [14].

Other interactions of Edg1

• Furthermore, DHS1P was as potent as S1P in activating ERK in control C6 cells, a pattern also observed in cells overexpressing Edg-1 [3].

Analytical, diagnostic and therapeutic context of Edg1

• Immunosuppressive activity of FTY720, sphingosine 1-phosphate receptor agonist: I. Prevention of allograft rejection in rats and dogs by FTY720 and FTY720-phosphate [15].

References