ライフサイエンスコーパス: EDG

1 EDG-1 bound SPP with high affinity (dissociation constan

2 EDG-1 expression also profoundly enhanced the migratory

3 EDG-1 is a G protein-coupled receptor for sphingosine 1-

4 EDG-1 is a heterotrimeric guanine nucleotide binding pro

5 EDG-1 mRNA but not EDG-3 mRNA was rapidly induced relati

6 EDG-1, -2, -3, -5, -6, and -7, but not -8, mRNAs were ex

7 EDG-1, -3, -5, -6, and -8 bind the bioactive lipid sphin

8 EDG-1, an inducible G-protein-coupled receptor from vasc

9 EDG-2, -4, and -7 bind the ligand lysophosphatidic acid.

10 EDG-4 mRNA was expressed in mouse islets.

11 EDG-6 is a recently cloned member of the endothelial dif

12 evels of endothelial differentiation gene 1 (EDG-1), which mediates the egress of T lymphocytes from

13 S1P(1)/EDG-1 receptor expression was similar in both types of V

14 on G protein-coupled receptors of the S1P(1)/EDG-1 subfamily.

15 hingosine-1-phosphate (SPP) receptors EDG-1, EDG-3, and EDG-5 and lysophosphatidic acid (LPA) recepto

16 to and signals through SPP receptors EDG-1, EDG-3, and EDG-5, had no effect on chemotactic motility

17 H218/AGR16/EDG-5, LP(B3)/EDG-3, LP(B4)/NRG-1/EDG-8, and LP(C1)/EDG-6.

18 ously, three cognate LPA GPCRs (LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7) were identified i

19 ied as mammalian LPA receptors: LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7.

20 e co-expression of mRNAs encoding the EDG-2, EDG-4, and PSP24 receptors in a variety of cell lines an

21 ognate LPA GPCRs (LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7) were identified in mammals.

22 an LPA receptors: LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7.

23 LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7) were identified in mammals.

24 LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7.

25 Moreover, PDGF activated EDG-1, as measured by translocation of beta-arrestin and

26 ense phosphothioate oligonucleotides against EDG-1 as well as EDG-3 receptors.

27 in mammals: LP(B1)/EDG-1, LP(B2)/H218/AGR16/EDG-5, LP(B3)/EDG-3, LP(B4)/NRG-1/EDG-8, and LP(C1)/EDG-

28 In agreement, EDG-8 did not stimulate phosphoinositide turnover or cAM

29 ), which express the SPP receptors EDG-1 and EDG-3, while higher concentrations of SPP were less effe

30 evels of EDG-3, neither expressed EDG-1, and EDG-5 mRNA was expressed in MCF-7 but not in MDA-MB-231

31 Both EDG-1-and EDG-3-regulated signaling pathways are required for endo

32 ]GTPgammaS binding assays of the 5HT(1A) and EDG(1) GPCRs confirmed that they were properly folded an

33 ophosphatidic acid (LPA) receptors EDG-2 and EDG-4 suggested that its ligand may be a lysophospholipi

34 e expression of the LPA receptors, EDG-2 and EDG-4, which are significantly upregulated in the inner

35 Microinjection of the EDG-3 and EDG-5 but not EDG-1 mRNA conferred SPP-responsive intrac

36 -phosphate (SPP) receptors EDG-1, EDG-3, and EDG-5 and lysophosphatidic acid (LPA) receptors EDG-2 an

37 nals through SPP receptors EDG-1, EDG-3, and EDG-5, had no effect on chemotactic motility of MDA-MB-2

38 co-injection also potentiated the EDG-5 and EDG-3 mediated responses to SPP.

39 The cooperation of EGW and EDG in diaryl-substituted alkynes did not lead to any in

40 Both EWG and EDG meta-substituted aryls preferred the beta-regioisome

41 CCR7 mediates entry into the lymph nodes and EDG-1 signaling controls their subsequent exit.

42 In the present study, the effects of S1P and EDG/S1P receptor expression were determined in rat VSM f

43 ns, inhibited chemotaxis of both vector- and EDG-1-overexpressing HEK293 cells.

44 (human or mouse)-specific anti-CD31 and anti-EDG mAbs including an antihuman EDG mAb termed SN6h.

45 idity and in vivo antitumor efficacy of anti-EDG mAbs and suggest the importance of other factors (e.

46 The present three anti-EDG monoclonal antibodies (mAbs), SN6f, SN6j, and SN6k,

47 D31 and anti-EDG mAbs including an antihuman EDG mAb termed SN6h.

48 t systemic administration of naked antihuman EDG mAbs can suppress established tumors, and the effica

49 otein-coupled receptor S1P(1) (also known as EDG-1).

50 rotein-coupled receptor NRG-1, also known as EDG-8, binds sphingosine-1-phosphate (S1P) with high aff

51 te oligonucleotides against EDG-1 as well as EDG-3 receptors.

52 tors have been identified in mammals: LP(B1)/EDG-1, LP(B2)/H218/AGR16/EDG-5, LP(B3)/EDG-3, LP(B4)/NRG

53 P(B1)/EDG-1, LP(B2)/H218/AGR16/EDG-5, LP(B3)/EDG-3, LP(B4)/NRG-1/EDG-8, and LP(C1)/EDG-6.

54 Both EDG-1-and EDG-3-regulated signaling pathways are require

55 Interestingly, both EDG-1 and -3 receptors were required for Rho activation.

56 to be highly stable in the presence of both EDG and EWG substituents.

57 novel molecular locus for eNOS activation by EDG receptors in vascular endothelial cells.

58 LP(B3)/EDG-3, LP(B4)/NRG-1/EDG-8, and LP(C1)/EDG-6.

59 l boronic acids or pinacol esters containing EDG were converted in good yields and fast reactions to

60 fine a novel signaling pathway that controls EDG-1 up-regulation following stimulation of T cells by

61 GFbetaR and EGFR was mediated via Gi-coupled EDG receptors.

62 ls mediated by a family of G protein-coupled EDG receptors.

63 sis, via the activation of G protein-coupled EDG receptors.

64 , transiently transfected with cDNA encoding EDG-6.

65 Endoglin (EDG; CD105) is a proliferation-associated cell membrane

66 hamster ovary cells that expressed exogenous EDG-1, activation of Akt and ERK1/2 in response to S1P w

67 n of adult-medial VSMCs expressing exogenous EDG-1 required G(i) activation but not p70 S6 kinase.

68 moderate levels of EDG-3, neither expressed EDG-1, and EDG-5 mRNA was expressed in MCF-7 but not in

69 on in Chinese hamster ovary cells expressing EDG-8 but not empty vector.

70 In co-transfection experiments expressing EDG-1 and eNOS cDNAs in COS-7 cells, we found that S1P t

71 amster ovary cells heterologously expressing EDG-8, S1P inhibited forskolin-induced cAMP accumulation

72 the endothelial differentiation gene family (EDG) of receptors and leads to diverse signaling events

73 ructurally related to SPP, is an agonist for EDG-1.

74 ggest that LPA is a low-affinity agonist for EDG-1.

75 med by sphingosine kinase, is the ligand for EDG-1, a GPCR important for cell migration and vascular

76 -ischemia and retinal tissue was stained for EDG receptors.

77 Furthermore, EDG is essential for angiogenesis and a component of the

78 tility via endothelial differentiation gene (EDG) family G protein-coupled receptors.

79 identified endothelial differentiation gene (EDG) family of G protein-coupled SPP receptors.

80 ber of the endothelial differentiation gene (EDG) G protein-coupled receptor family that is expressed

81 The endothelial differentiation gene (EDG) receptors are a class of G protein-coupled receptor

82 ) specific endothelial differentiation gene (EDG) receptors have been implicated in various anti-apop

83 ion of the endothelial differentiation gene (EDG/S1P) family of 7 transmembrane G protein-coupled rec

84 rom tonsil PCs (early differentiation genes [EDGs]), and tonsil PCs from bone marrow PCs (late differ

85 ion of the G protein-coupled receptor (GPCR) EDG-1.

86 the arenes bearing electron-donating groups (EDG) are either negligible or slightly repulsive, while

87 g groups (EWG) and electron-donating groups (EDG) have opposite effects on the rate such that k(EWG)

88 egative values for electron-donating groups (EDGs).

89 However, EDG-1 appears to be dispensable for mitogenicity and sur

90 erived growth factor (PDGF) are abrogated in EDG-1 null fibroblasts.

91 t activation of p70 S6 kinase is critical in EDG-1/G(i)-mediated cell proliferation.

92 tracellular signal-regulated kinase (Erk) in EDG-6 transfected cells in a pertussis toxin-sensitive m

93 agonized SPP-activated calcium transients in EDG-3 expressing oocytes with an IC50 of 22 microM, sugg

94 ys in RH7777 cells expressing the individual EDG-family GPCRs.

95 for 7 days, the relative levels of rat islet EDG-1 mRNA were significantly reduced to 54% below that

96 ite effects on the rate such that k(EWG) > k(EDG).

97 icroinjection of the EDG-3 and EDG-5 but not EDG-1 mRNA conferred SPP-responsive intracellular calciu

98 EDG-1 mRNA but not EDG-3 mRNA was rapidly induced relative to 18S rRNA afte

99 ulatory functions in the apparent absence of EDG S1P receptor homologues.

100 2, p38, were dysregulated in the absence of EDG-1.

101 We analyzed the subcellular distribution of EDG-1 in COS-7 cells transiently transfected with cDNA c

102 We examined the expression of EDG receptors in a model of retinal ischemia-reperfusion

103 results suggest that enhanced expression of EDG-1 in VSMCs dramatically stimulates both the prolifer

104 Co-expression of EDG-1 receptor with the chimeric Galphaqi protein confer

105 The increased expression of EDG-1 was preceded by up-regulation of its transcription

106 cellular SPP, was dependent on expression of EDG-1.

107 Homology of EDG-6 to the known sphingosine-1-phosphate (SPP) recepto

108 activation of eNOS and Akt independently of EDG-1 receptor transfection.

109 t pup-intimal VSMCs express higher levels of EDG-1 mRNA than adult-medial VSMCs.

110 and MCF-7 cells expressed moderate levels of EDG-3, neither expressed EDG-1, and EDG-5 mRNA was expre

111 Overexpression of EDG-1 induced exaggerated cell-cell aggregation, enhance

112 ttenuated agonist-induced phosphorylation of EDG-1 receptor by >90%.

113 tion of beta-arrestin and phosphorylation of EDG-1.

114 lts may also shed light on the vital role of EDG-1 in vascular maturation.

115 Stimulation of EDG receptors by S1P has been shown to activate the endo

116 Stimulation of EDG receptors in islets and INS-1 cells with SPP inhibit

117 The agonist-modulated targeting of EDG-1 to caveolae and its dynamic inhibitory interaction

118 gh the S1P pathway, even as the targeting of EDG-1 to caveolae facilitates the interactions of this r

119 The targeting of EDG-1 to caveolae-enriched fractions was markedly increa

120 ically induces the reversible trafficking of EDG-1 via the endosomal pathway and that the C-terminal

121 Transactivation of EDG-1 by Akt is not required for G(i)-dependent signalin

122 Stable transfection of EDG-1 into adult-medial VSMCs enhanced their proliferati

123 to have dramatically variable expression of EDGs and LDGs, and one-way analysis of variance (ANOVA)

124 for those compounds bearing arenes with one EDG and one EWG.

125 Furthermore, because only EDG-3 was antagonized by suramin, variations in receptor

126 hereas INS-1 insulinoma cells expressed only EDG-1, -2, -3, and -5 mRNAs.

127 dothelial-derived G-protein-coupled receptor EDG-1 is a high-affinity receptor for the bioactive lipi

128 Activation of the endothelial receptor EDG-1 by platelet-derived lipids LPA and SPP may be impo

129 protein (G protein)-coupled orphan receptor EDG-1, originally cloned as Endothelial Differentiation

130 xpressing the G protein-coupled SPP receptor EDG-1.

131 -5 and lysophosphatidic acid (LPA) receptors EDG-2 and EDG-4 suggested that its ligand may be a lysop

132 ells (BAEC), which express the SPP receptors EDG-1 and EDG-3, while higher concentrations of SPP were

133 h binds to and signals through SPP receptors EDG-1, EDG-3, and EDG-5, had no effect on chemotactic mo

134 nown sphingosine-1-phosphate (SPP) receptors EDG-1, EDG-3, and EDG-5 and lysophosphatidic acid (LPA)

135 a baseline expression of the LPA receptors, EDG-2 and EDG-4, which are significantly upregulated in

136 There was no change in relative EDG-3 mRNA levels.

137 for 2 h with 17 mmol/l glucose, the relative EDG-1 mRNA levels increased almost twofold compared with

138 In agreement with the literature reports, EDG para-substituted aryls, to some extent, favored the

139 athways that modulate eNOS regulation by S1P/EDG in vascular endothelial cells remain less well under

140 te Akt activation and eNOS regulation by S1P/EDG receptors.

141 let-derived sphingolipid that binds to S1P1 (EDG-1) receptors and activates the endothelial isoform o

142 d that the expression of S1P3/EDG-3 and S1P2/EDG-5 receptors is 4-fold higher in cerebral artery comp

143 ibodies revealed that the expression of S1P3/EDG-3 and S1P2/EDG-5 receptors is 4-fold higher in cereb

144 Since EDG-1 is expressed in the pup-intimal phenotype of VSMCs

145 G-protein-coupled receptors (GPCRs) for SPP, EDG-1, -3, and -5 are characterized using a Xenopus oocy

146 dynamics and subcellular localization of SPP-EDG-1 interaction.

147 f SPP may spatially and temporally stimulate EDG-1, resulting in activation and integration of downst

148 with cDNA constructs encoding epitope-tagged EDG-1.

149 triphosphate binding assay demonstrates that EDG-8 activated G(i/o) and G12 but not Gs and G(q/11) in

150 These results indicate that EDG-6 is a high affinity receptor for SPP, which couples

151 Our results indicate that EDG-8, a member of the EDG-1 subfamily, couples to uniqu

152 apoptosis, which raises the possibility that EDG receptors participate in anti-apoptotic signaling in

153 -immunoprecipitation experiments showed that EDG-1 could be specifically precipitated by antibodies d

154 Our results suggest that EDG-1 functions as an integrator linking the PDGFR to la

155 xpression and proliferation, suggesting that EDG-1-coupling to the G(i) pathway is critical.

156 The EDG-1-GFP-containing vesicles are distinct from mitochon

157 telet-derived bioactive lipid, activates the EDG-1 and -3 subtypes of G protein-coupled receptors on

158 tration well below the potency of LPA at the EDG-1 receptor.

159 in kinase C inhibitor GF 109203X blocked the EDG-1 induction by PMA.

160 In the present study, we constructed the EDG-1-green fluorescent protein (GFP) chimera to examine

161 cate the co-expression of mRNAs encoding the EDG-2, EDG-4, and PSP24 receptors in a variety of cell l

162 o induce mitogenesis in cells expressing the EDG-1 subfamily of G protein-coupled receptors is well c

163 cently been identified as the ligand for the EDG family of G protein-coupled cell surface receptors.

164 ate (S1P), a platelet-derived ligand for the EDG-1 family of G protein-coupled receptors (GPCRs), has

165 g that it is an antagonist selective for the EDG-3 GPCR isotype.

166 eNOS in BAEC in a pathway distinct from the EDG-1 receptor, but mediated by a similar receptor-media

167 tracellular calcium transients; however, the EDG-5 response was quantitatively much less.

168 l surface G protein-coupled receptors of the EDG family and induces profound effects in a variety of

169 ients revealed that approximately 55% of the EDG-1 protein was recovered in fractions enriched in cav

170 results suggest that the interaction of the EDG-1 receptor with caveolin may serve to inhibit signal

171 results indicate that EDG-8, a member of the EDG-1 subfamily, couples to unique signaling pathways.

172 Microinjection of the EDG-3 and EDG-5 but not EDG-1 mRNA conferred SPP-respons

173 or Galphaq co-injection also potentiated the EDG-5 and EDG-3 mediated responses to SPP.

174 In endothelial cells, S1P stimulates the EDG-1 receptor-mediated activation of the endothelial is

175 Here we show that SPP signals through the EDG-1 receptor to the heterotrimeric G protein G(i), lea

176 kidney 293 cells stably transfected with the EDG-1-GFP cDNA expressed the receptor primarily on the p

177 Thus, EDG receptors are expressed in pancreatic islet beta-cel

178 In addition, LPA binding to EDG-1 induces receptor phosphorylation, mitogen-activate

179 SPP stimulates cell migration by binding to EDG-1.

180 sylphosphorylcholine competed for binding to EDG-6, but only at very high concentrations.

181 Activated Akt binds to EDG-1 and phosphorylates the third intracellular loop at

182 LPA binds to EDG-1 receptor with an apparent Kd of 2.3 microM.

183 SPP binds to EDG-1-GFP and transduces intracellular signals in a mann

184 of ERK5(flox/flox)/Lck-Cre murine T cells to EDG-1 ligands.

185 naive T cells showed increased migration to EDG-1 ligands at 48 h, the migration of ERK5(flox/flox)/

186 pathways regulated by the binding of S1P to EDG-8.

187 NOVA) was used to identify the most variable EDGs (vEDGs) and LDGs (v1LDG and v2LDG).

188 ntimal phenotype of VSMCs, S1P signaling via EDG-1 may play a role in vascular diseases in which the

189 After SPP washout, EDG-1-GFP recycles back to the plasma membrane with a ta

190 of transfected caveolin-1 cDNA together with EDG-1 and eNOS markedly diminished S1P-mediated eNOS act

191 Fenton-like systems driven by 1,2-DHBs with EDGs depends only on the Fe(III) reduction mediated by 1