Disease relevance of EDG8

• In this study, the expression and localization of cornifin-alpha/SPPR1 was examined in untreated and tumor promoter-treated mouse skin, hair follicles, and skin neoplasms [1].

High impact information on EDG8

• Our results indicate that EDG-8, a member of the EDG-1 subfamily, couples to unique signaling pathways [2].
• In this paper we examined the signal transduction pathways regulated by the binding of S1P to EDG-8 [2].
• The previously cloned rat nerve growth factor-regulated G protein-coupled receptor NRG-1 (Glickman, M., Malek, R. L., Kwitek-Black, A. E., Jacob, H. J., and Lee N. H. (1999) Mol. Cell. Neurosci. 14, 141-52), also known as EDG-8, binds sphingosine-1-phosphate (S1P) with high affinity and specificity [2].
• In agreement, EDG-8 did not stimulate phosphoinositide turnover or cAMP accumulation [2].
• A subunit selective [35S] guanosine 5'-3-O-(thio)triphosphate binding assay demonstrates that EDG-8 activated G(i/o) and G12 but not Gs and G(q/11) in response to S1P [2].

Biological context of EDG8

• The four SPP receptor subtypes regulate different intracellular signal transduction pathways [3].
• Surprisingly, we found that low concentrations of SPP (10-100 nM) increased chemotaxis of HEK293 cells overexpressing the G protein-coupled SPP receptor EDG-1 [4].
• At 24 weeks of gestation, fragments of radial glial fibers are Edg-8-positive within the cortical plate and subplate of allocortical areas [5].

Anatomical context of EDG8

• 1 (Edg 1), 2 (Edg 5), 3 (Edg 3), 4 (Edg 6), and 5 (Edg 8) mRNA in keratinocytes was identified [6].
• These Edg-8-positive fragments often appear enlarged as varicosities and some of them terminate at blood vessels [5].
• After 32 weeks of gestation, radial glial fibers gradually disappear; instead Edg-8-positive transitional stages between radial glia and astrocytes were found [5].
• In conclusion, PLD is one of the signalling components linking SPP-receptor activation to assembly of actin stress fibres [7].

Associations of EDG8 with chemical compounds

• In Chinese hamster ovary cells heterologously expressing EDG-8, S1P inhibited forskolin-induced cAMP accumulation and activated c-Jun NH2-terminal kinase [2].

Other interactions of EDG8

• S1P1 expression was weak, and no significant expression of either S1P4 or S1P5 was detected [8].
• Characterization of a human sphingosine-1-phosphate receptor gene (S1P5) and its differential expression in LGL leukemia [9].
• Recently, cornifin-alpha/SPPR1 has been identified as a putative precursor protein of the cornified cell envelope [1].

References