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Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation
Liu Y.3; Wada R.3; Yamashita T.3; Mi Y.3; Deng C.-X.3; Hobson J.P.4; Rosenfeldt H.M.4; Nava V.E.4; Chae S.-S.2; Lee M.-J.2; Liu C.H.2; Hla T.2; Spiegel S.4; Proia R.L.3
2000
Source PublicationJournal of Clinical Investigation
ISSN00219738
Volume106Issue:8Pages:951-961
Abstract

Sphingolipid signaling pathways have been implicated in many critical cellular events. Sphingosine-1-phosphate (SPP), a sphingolipid metabolite found in high concentrations in platelets and blood, stimulates members of the endothelial differentiation gene (Edg) family of G protein-coupled receptors and triggers diverse effects, including cell growth, survival, migration, and morphogenesis. To determine the in vivo functions of the SPP/Edg signaling pathway, we disrupted the Edg1 gene in mice. Edg1(-/-) mice exhibited embryonic hemorrhage leading to intrauterine death between E12.5 and E14.5. Vasculogenesis and angiogenesis appeared normal in the mutant embryos. However, vascular maturation was incomplete due to a deficiency of vascular smooth muscle cells/pericytes. We also show that Edg-1 mediates an SPP-induced migration response that is defective in mutant cells due to an inability to activate the small GTPase, Rac. Our data reveal Edg-1 to be the first G protein-coupled receptor required for blood vessel formation and show that sphingolipid signaling is essential during mammalian development.

DOI10.1172/JCI10905
URLView the original
Indexed BySCI
Language英语
WOS Research AreaResearch & Experimental Medicine
WOS SubjectResearch & Experimental Medicine
WOS IDWOS:000089919700007
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Cited Times [WOS]:828   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionPersonal research not belonging to the institution
Corresponding AuthorProia R.L.
Affiliation1.National Institutes of Health, Bethesda
2.University of Connecticut Health Center
3.National Institute of Diabetes and Digestive and Kidney Diseases
4.Georgetown University Medical Center
Recommended Citation
GB/T 7714
Liu Y.,Wada R.,Yamashita T.,et al. Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation[J]. Journal of Clinical Investigation,2000,106(8):951-961.
APA Liu Y..,Wada R..,Yamashita T..,Mi Y..,Deng C.-X..,...&Proia R.L..(2000).Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation.Journal of Clinical Investigation,106(8),951-961.
MLA Liu Y.,et al."Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation".Journal of Clinical Investigation 106.8(2000):951-961.
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