Disease relevance of EDG5

• Moreover, S1P1, S1P3 and S1P2 receptors are expressed in the majority of human glioblastomas as determined by reverse transcriptase-polymerase chain reaction analysis [1].
• Trancriptional activation of reporter genes for the c-fos promoter and the serum response element by Edg3 and Edg5 transfected in Jurkat cells was inhibited by pertussis toxin and C3 exoenzyme, implicating G(i/o)- and Rho-dependent pathways [2].
• RESULTS: Northern blotting analysis has revealed that S1P2 was expressed in all gastric cancer cell lines to varying degrees, and S1P3 was expressed in four cell lines [3].
• When H218 and Edg3 were stably expressed in rat HTC4 hepatoma cells, S1P induced Ca2+ responses with nanomolar EC50 values [4].
• Astrocytomas of various histologic grades expressed three types of sphingosine-1-phosphate receptors, S1P1, S1P2, and S1P3; however, no significant correlation with histologic grade or patient survival was detected [5].

High impact information on EDG5

• S1P induced comparable increases in the amounts of GTP-RhoA in EDG3 and EDG5 cells [6].
• Actin staining of S1P stimulated U118 cells overexpressing beta-galactosidase resulted in pronounced stress fiber formation that was exacerbated by S1P2 overexpression, partially blocked by S1P1, or totally abolished by pretreatment with Y-27632 [7].
• S1P-mediated inhibition correlated with S1P2 receptor expression [7].
• FTY720-P, an S1P analogue that binds all S1P receptors except S1P2, did not inhibit glioblastoma cell migration [7].
• Our data also indicated that Edg3 and Edg5 mediated the serum response element activation through transcriptional factors Elk-1 and serum response factor [2].

Biological context of EDG5

• Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5 [2].
• Transfection of HEK293 cells with H218 or edg-3, but not edg-1, induces rounded cell morphology in the presence of serum, which contains high levels of SPP [8].
• Northern analysis revealed that brain H218 mRNA is preferentially expressed during embryogenesis [9].
• No individuals with the S1P2 haplotype were observed due to an extreme linkage disequilibrium between the two RFLP loci [10].
• Chromosomal mapping employing a rat somatic cell readiation hybrid panel demonstrated that nrg-1 is linked to marker D8Rat54 and tightly associated with H218 on chromosome 8 [11].

Anatomical context of EDG5

• Consistent with angiogenesis in general during decidualization, we believe EDG1 and EDG5 to be regulated by the embryo because no microvascular expression for these receptors was observed in oil-induced deciduomas [12].
• Unlike EDG3 and EDG5, which are expressed in the smooth muscle cell layer of the human aorta, no signal corresponding to EDG1 expression could be detected in the aorta [13].
• Nerve growth factor-induced neuritogenesis in PC12 cells was inhibited by overexpression of H218 and to a lesser extent Edg-3 [8].
• Thus, H218, and possibly Edg-3, may be the cell surface receptors responsible for cell rounding and neurite retraction induced by SPP [8].
• We showed that H218 and Edg3 were capable of mediating S1P-induced mobilization of intracellular Ca2+ when transiently transfected in human TAg-Jurkat T cells [4].

Associations of EDG5 with chemical compounds

• EDG3 is a functional receptor specific for sphingosine 1-phosphate and sphingosylphosphorylcholine with signaling characteristics distinct from EDG1 and AGR16 [14].
• Additionally, EDG3 mediated a decrease in cellular cyclic AMP content, like EDG1, but contrasting with AGR16 which mediated an increase in cyclic AMP [14].
• In contrast to SPP, sphinganine-1-phosphate, which binds to and signals through SPP receptors EDG-1, EDG-3, and EDG-5, had no effect on chemotactic motility of MDA-MB-231 or MCF-7 cells [15].
• Moreover, an antisense ODN designed to inhibit Edg5 expression also decreased the SPP-induced rise in Ca(2+), although to a lesser extent than that observed by inhibiting Edg3 [16].

Analytical, diagnostic and therapeutic context of EDG5

• Polymerase chain reaction techniques and medium stringency library screening were used to isolate a rat cDNA ("H218") which encodes a novel guanine nucleotide-binding protein coupled receptor homolog ("pH218") [9].

References