Disease relevance of Edg1

• Edg1(-/-) mice exhibited embryonic hemorrhage leading to intrauterine death between E12.5 and E14 [1].
• Sphingosine-1-phosphate receptor subtype-specific positive and negative regulation of Rac and haematogenous metastasis of melanoma cells [2].
• Regulation of limb development by the sphingosine 1-phosphate receptor S1p1/EDG-1 occurs via the hypoxia/VEGF axis [3].
• Binding of SPP to Edg-1 resulted in inhibition of forskolin-stimulated cAMP accumulation, in a pertussis toxin-sensitive manner [4].
• Finally, SPP suppresses apoptosis of HL-60 and pheochromocytoma PC12 cells, which do not have specific SPP binding or expression of Edg-1 mRNA [4].

High impact information on Edg1

• Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility [5].
• Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization [6].
• The net result of endothelial cell S1P1 receptor activation is the proper trafficking and strengthening of N-cadherin-dependent cell-cell adhesion with mural cells [6].
• Endothelial cell S1P1/Gi/Rac pathway induces microtubule polymerization, resulting in trafficking of N-cadherin to polarized plasma membrane domains [6].
• Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone [7].

Chemical compound and disease context of Edg1

• FTY720, sphingosine 1-phosphate receptor modulator, ameliorates experimental autoimmune encephalomyelitis by inhibition of T cell infiltration [8].

Biological context of Edg1

• Inhibitory and stimulatory regulation of Rac and cell motility by the G12/13-Rho and Gi pathways integrated downstream of a single G protein-coupled sphingosine-1-phosphate receptor isoform [9].
• Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate [10].
• Although transactivation of S1P1 and Gi signaling are important for cytoskeletal rearrangements and migration of mast cells toward antigen, they are dispensable for FcepsilonRI-triggered degranulation [11].
• Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference [12].
• The phenotype of the conditional mutant embryos mimicked the one obtained in the embryos globally deficient in S1P1 [13].

Anatomical context of Edg1

• A deletion mutant lacking the N-terminal processing domain of Edg-1/S1P1 accumulated in the endoplasmic reticulum, and was not expressed on the cell surface [14].
• We found expression of S1P1, S1P2, and S1P3 receptors on NOD aortic endothelial cells [15].
• Sphingosine-1 Phosphate Prevents Monocyte/Endothelial Interactions in Type 1 Diabetic NOD Mice Through Activation of the S1P1 Receptor [15].
• The S1P1 receptor-specific agonist SEW2871 inhibited monocyte adhesion to diabetic aortas [15].
• Indeed, CD4+/CD25+ T cells express lower levels of S1P1 and S1P4 receptors and demonstrate a reduced chemotactic response to S1P [16].

Associations of Edg1 with chemical compounds

• The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis [17].
• Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are extracellular ligands for a family of G protein-coupled receptors (GPCRs), LPA1/2/3 and S1P1/2/3/4/5 [18].
• The sphingosine 1-phosphate receptor agonist FTY720 differentially affects the sequestration of CD4+/CD25+ T-regulatory cells and enhances their functional activity [16].
• Similarly, S1P-elicited threonine phosphorylation of S1P1 Rs was suppressed by a selective inhibitor of PKCepsilon after 24 h, but not 1 h [19].
• Tyrosine sulfation of S1P1 may be a major controller of S1P effects on T cell traffic [20].
• S1P-mediated activation of ERK or Akt was not diminished but inhibition of cAMP accumulation by S1P and SEW2871 was abolished by MbetaCD treatment [21].

Regulatory relationships of Edg1

• These results indicate that FTY720- and sphingosine 1-phosphate receptor-stimulated T cell migration are dependent on the restricted usage of chemokine receptor-ligand pairs within discrete anatomic compartments [22].
• However, administration of FTY720, a sphingosine 1-phosphate receptor modulator that induces CD62L-independent T cell accumulation in the LNs, restored CD4(+)CD25(+) Treg in the LNs along with graft survival [23].
• By simultaneously upregulating S1P1 and downregulating CCR7, T cells that have divided multiple times switch to a state favoring egress over retention [24].

Other interactions of Edg1

• Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation [1].
• Inhibition of Th1- and Th2-mediated airway inflammation by the sphingosine 1-phosphate receptor agonist FTY720 [25].

Analytical, diagnostic and therapeutic context of Edg1

• In a comparison of embryonic brain expression patterns of lysophosphatidic acid and sphingosine 1-phosphate receptor genes (lpa(1-3) and s1p(1-5), respectively), transcripts detected by Northern blot were subsequently localized using in situ hybridization [26].
• Adoptive cell transfer experiments establish an intrinsic requirement for S1P1 in T and B cells for lymphoid organ egress [27].
• Microarray analysis revealed downregulation of further endothelial specific transcripts after S1P1 silencing [28].
• These data have important implications for targeting the sphingosine 1-phosphate receptor 1 in solid organ transplantation [29].
• Immunoelectron microscopy revealed that intranodal lymphocytes lacked surface expression of S1P1, whereas S1P1 was evident on the surface and within the cytoplasm of macrophages, endothelial cells, and stromal cells [30].

References