Molecular Cloning of a Novel Putative G Protein-Coupled Receptor Expressed in the Cardiovascular System

Okazaki, Hiroshi; Ishizaka, Noriko; Sakurai, Takeshi; Kurokawa, Kenji; Goto, Kaoru; Kumada, Mamoru; Takuwa, Yoh

doi:10.1006/bbrc.1993.1163

Cited by 145 publications

(94 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…independent of its e ects on RBF. Moreover, mRNA for Edg-1 and Edg-3 SPP receptors is present in rat and human kidney Lado et al, 1994;Okazaki et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Lysosphingolipid receptor‐mediated diuresis and natriuresis in anaesthetized rats

Bischoff

Heringdorf

Jakobs

et al. 2001

British J Pharmacology

View full text Add to dashboard Cite

1 Lysosphingolipids such as sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPPC) can act on speci®c G-protein-coupled receptors. Since SPP and SPPC cause renal vasoconstriction, we have investigated their e ects on urine and electrolyte excretion in anaesthetized rats. 2 Infusion of SPP (1 ± 30 mg kg 71 min 71 ) for up to 120 min dose-dependently but transiently (peak after 15 min, disappearance after 60 min) reduced renal blood¯ow without altering endogenous creatinine clearance. Nevertheless, infusion of SPP increased diuresis, natriuresis and calciuresis and, to a lesser extent, kaliuresis. These tubular lysosphingolipid e ects developed more slowly (maximum after 60 ± 90 min) and also abated more slowly upon lysosphingolipid washout than the renovascular e ects. 3 Infusion of SPPC, sphingosine and glucopsychosine (3 ± 30 mg kg 71 min 71 each) caused little if any alterations in renal blood¯ow but also increased diuresis, natriuresis and calciuresis and, to a lesser extent, kaliuresis. 4 Pretreatment with pertussis toxin (10 mg kg 71 3 days before the acute experiment) abolished the renovascular and tubular e ects of 30 mg kg 71 min 71 SPP. 5 These ®ndings suggest that lysosphingolipids are a hitherto unrecognized class of endogenous modulators of renal function. SPP a ects renovascular tone and tubular function via receptors coupled to G i -type G-proteins. SPPC, sphingosine and glucopsychosine mimic only the tubular e ects of SPP, and hence may act on distinct sites.

show abstract

“…independent of its e ects on RBF. Moreover, mRNA for Edg-1 and Edg-3 SPP receptors is present in rat and human kidney Lado et al, 1994;Okazaki et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Lysosphingolipid receptor‐mediated diuresis and natriuresis in anaesthetized rats

Bischoff

Heringdorf

Jakobs

et al. 2001

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…EDG1, EDG3, and EDG5 cDNAs were described previously (20,51,53). The expression vectors for V 12 -Rac1, myc-tagged V 12 -Rac1, N 17 -Rac1, myc-tagged N 17 -Rac1, myc-tagged wild-type Rac1, and myctagged PAK1 (pME18S-V 12 -Rac1, pME18S-myc-V 12 -Rac1, pME18S-N 17 -Rac1, pME18S-myc-N 17 -Rac1, pME18S-myc-Rac1, and pCMV6M-PAK1, respectively) were described previously (17,48,64,67).…”

Section: Methodsmentioning

confidence: 99%

“…Among the EDG receptors, EDG1, EDG3, EDG5 (AGR16 or H218), and EDG8 are identified as receptors specific for S1P (8,20,30,34,35,44,46,47,49,65,66,71), while EDG2, EDG4, and EDG7 are receptors specific for LPA (5,15,26,49). EDG1, EDG3, and EDG5 are widely expressed in various tissues (25,53,76), whereas expression of EDG8 is confined to the central nervous system (30). We and others have shown that the S1P receptors exhibit distinct signaling characteristics.…”

mentioning

confidence: 99%

Inhibitory Regulation of Rac Activation, Membrane Ruffling, and Cell Migration by the G Protein-Coupled Sphingosine-1-Phosphate Receptor EDG5 but Not EDG1 or EDG3

Okamoto

Takuwa

Yokomizo

et al. 2000

Molecular and Cellular Biology

306

303

View full text Add to dashboard Cite

Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that induces a variety of biological responses in diverse cell types. Many, if not all, of these responses are mediated by members of the EDG (endothelial differentiation gene) family G protein-coupled receptors EDG1, EDG3, and EDG5 (AGR16). Among prominent activities of S1P is the regulation of cell motility; S1P stimulates or inhibits cell motility depending on cell types. In the present study, we provide evidence for EDG subtype-specific, contrasting regulation of cell motility and cellular Rac activity. In CHO cells expressing EDG1 or EDG3 (EDG1 cells or EDG3 cells, respectively) S1P as well as insulin-like growth factor I (IGF I) induced chemotaxis and membrane ruffling in phosphoinositide (PI) 3-kinase-and Rac-dependent manners. Both S1P and IGF I induced a biphasic increase in the amount of the GTP-bound active form of Rac. In CHO cells expressing EDG5 (EDG5 cells), IGF I similarly stimulated cell migration; however, in contrast to what was found for EDG1 and EDG3 cells, S1P did not stimulate migration but totally abolished IGF I-directed chemotaxis and membrane ruffling, in a manner dependent on a concentration gradient of S1P. In EDG5 cells, S1P stimulated PI 3-kinase activity as it did in EDG1 cells but inhibited the basal Rac activity and totally abolished IGF I-induced Rac activation, which involved stimulation of Rac-GTPase-activating protein activity rather than inhibition of Rac-guanine nucleotide exchange activity. S1P induced comparable increases in the amounts of GTP-RhoA in EDG3 and EDG5 cells. Neither S1P nor IGF I increased the amount of GTP-bound Cdc42. However, expression of N 17 -Cdc42, but not N 19 -RhoA, suppressed S1P-and IGF I-directed chemotaxis, suggesting a requirement for basal Cdc42 activity for chemotaxis. Taken together, the present results demonstrate that EDG5 is the first example of a hitherto-unrecognized type of receptors that negatively regulate Rac activity, thereby inhibiting cell migration and membrane ruffling.

show abstract

“…[ [18][19][20]. Among these cDNAs, three kinds of orphan receptor cDNAs, Edg-1, Edg-3 and AGR16\H218 (Edg-5) have recently been identified as S1P receptors [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Sphingosine 1-phosphate stimulates proliferation and migration of human endothelial cells possibly through the lipid receptors, Edg-1 and Edg-3

Kimura

Watanabe

Sato

et al. 2000

Biochemical Journal

187

View full text Add to dashboard Cite

Sphingosine 1-phosphate (S1P) stimulates thymidine incorporation (DNA synthesis), cell growth and cell migration in human aortic endothelial cells (HAECs). The extent of the S1P-induced responses are comparable to those stimulated by vascular endothelial growth factor, one of the most potent stimulators of angiogenesis. These responses to S1P were mimicked by dihydrosphingosine 1-phosphate, an S1P receptor agonist, and inhibited by pertussis toxin (PTX), an inactivator of G i \G o -proteins. S1P also induced activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAP kinase). The activation of these enzymes was inhibited again by PTX and also by suramin, a non-selective receptor antagonist. S1P-induced DNA synthesis and ERK activation were inhibited

show abstract

Molecular Cloning of a Novel Putative G Protein-Coupled Receptor Expressed in the Cardiovascular System

Cited by 145 publications

References 0 publications

Lysosphingolipid receptor‐mediated diuresis and natriuresis in anaesthetized rats

Lysosphingolipid receptor‐mediated diuresis and natriuresis in anaesthetized rats

Inhibitory Regulation of Rac Activation, Membrane Ruffling, and Cell Migration by the G Protein-Coupled Sphingosine-1-Phosphate Receptor EDG5 but Not EDG1 or EDG3

Sphingosine 1-phosphate stimulates proliferation and migration of human endothelial cells possibly through the lipid receptors, Edg-1 and Edg-3

Contact Info

Product

Resources

About