Disease relevance of Edg5

• Upon inactivation of Gi by pertussis toxin, S1P3 mediated inhibition of Rac and migration just like S1P2 [1].
• Intriguingly, overexpression of S1P2 greatly potentiated the inhibition of metastasis by S1P, whereas that of S1P1 resulted in aggravation of metastasis [2].
• Ligand-dependent inhibition of B16 melanoma cell migration and invasion via endogenous S1P2 G protein-coupled receptor. Requirement of inhibition of cellular RAC activity [3].
• We present here Northern analysis indicating that the H218 mRNA is expressed in undifferentiated F9 embryonal carcinoma cells [4].

High impact information on Edg5

• In turn, S1P activates its receptors S1P1 and S1P2 that are present in mast cells [5].
• Overexpression of Galphai, by contrast, specifically antagonized S1P2-mediated inhibition of Rac and migration [1].
• The S1P2 actions were mimicked by expression of V14Rho and were abolished by C3 toxin and N19Rho, but not Rho kinase inhibitors [1].
• Treatment by various receptor-selective retinoids indicated that retinoic acid receptor beta or gamma signaling, but not retinoid X receptor activation, is required for the down-regulation of H218 mRNA [4].
• Activation of the H218 receptor may contribute to the phenotype of undifferentiated F9 embryonal carcinoma cells [4].

Biological context of Edg5

• It is expressed during embryogenesis, and mutation of an H218-like gene in zebrafish leads to profound defects in embryonic development [6].
• Notably, S1P2 overexpression increased the content of myogenic markers and hastened the onset of differentiated muscle phenotype in comparison with control cells [7].
• Down-regulation of EDG5/S1P2 during myogenic differentiation results in the specific uncoupling of sphingosine 1-phosphate signalling to phospholipase D [8].
• Negative regulation of endothelial morphogenesis and angiogenesis by S1P2 receptor [9].

Anatomical context of Edg5

• The data support a model in which SPP and SPC bind Edg-1 and/or Edg-5 receptors in osteoblasts leading to the release of Ca2+ from the ER through IP3-gated channels [10].
• We found expression of S1P1, S1P2, and S1P3 receptors on NOD aortic endothelial cells [11].
• This view was also supported by the marked reduction of S1P-induced PLD activity in myoblasts loaded with antisense oligodeoxyribonucleotides (ODN) to EDG5/S1P2 [8].
• Furthermore, overexpression of EDG5/S1P2 rescued the coupling of S1P signalling to PLD in C2C12 myotubes [8].

Associations of Edg5 with chemical compounds

• S1P, dihydro-S1P, and sphingosylphosphorylcholine inhibited B16 cell migration and invasion with the relative potencies expected as S1P2 receptor agonists [3].
• Sphingosine 1-phosphate regulates myogenic differentiation: a major role for S1P2 receptor [7].
• The H218 message is down-regulated and its stability is decreased during retinoic acid- and dibutyryl cAMP-induced differentiation [4].

Regulatory relationships of Edg5

• These results provide compelling evidence that endogenously expressed S1P2 negatively regulates cell motility and invasion through ligand-dependent reciprocal regulation of cellular Rac and RhoA activities [3].

Other interactions of Edg5

• Indeed, in differentiated cells a significant increase of EDG3/S1P3 together with a large decrease of EDG5/S1P2 expression at mRNA as well as protein level was detected [8].

References