Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.1.25 (
triphosphatase
)
1,529
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
EDG-1
is a heterotrimeric guanine nucleotide binding protein-coupled receptor (GPCR) for sphingosine-1-phosphate (SPP). Cell migration toward platelet-derived growth factor (PDGF), which stimulates sphingosine kinase and increases intracellular SPP, was dependent on expression of
EDG-1
. Deletion of edg-1 or inhibition of sphingosine kinase suppressed chemotaxis toward PDGF and also activation of the small guanosine
triphosphatase
Rac, which is essential for protrusion of lamellipodia and forward movement. Moreover, PDGF activated
EDG-1
, as measured by translocation of beta-arrestin and phosphorylation of
EDG-1
. Our results reveal a role for receptor cross-communication in which activation of a GPCR by a receptor tyrosine kinase is critical for cell motility.
...
PMID:Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. 1123 Jun 98
EDG-1
, encoded by the endothelial differentiation gene-1, is a heterotrimeric guanine nucleotide binding protein-coupled receptor (GPCR) for sphingosine-1-phosphate (SPP) that has been shown to stimulate angiogenesis and cell migration in cultured endothelial cells. Unexpectedly,
EDG-1
knockout embryos had a normal blood vessel network, vasculogenesis and angiogenesis, but died in utero owing to massive haemorrhaging as a result of failure of smooth muscle cells and pericytes to migrate around the circumference and reinforce endothelial tubes [Liu, Wada, Yamashita, Mi, Deng, Hobson, Rosenfeldt, Nava, Chae, Lee, et al. (2000) J. Clin. Invest. 106, 951-961]. This vascular maturation defect is similar to the phenotype of mice homozygous for disrupted alleles of platelet-derived growth factor B-subunit homodimer (PDGF-BB) or its receptor PDGFR-beta. We found that fibroblasts from
EDG-1
null embryos did not migrate toward PDGF or SPP, and inhibition of motility correlated with defective activation of the small guanosine
triphosphatase
Rac, which is required for lamellipodia formation and directional locomotion [Hobson, Rosenfeldt, Barak, Olivera, Poulton, Caron, Milstien, and Spiegel (2001) Science 291, 1800-1803]. Moreover, we showed that PDGF-directed cell migration requires both sphingosine kinase activation and expression of
EDG-1
, suggesting a functional link between PDGF signalling and
EDG-1
. Indeed, treatment of wild-type cells with PDGF transactivated
EDG-1
as determined by translocation of beta-arrestin and phosphorylation of
EDG-1
. These findings reveal a new paradigm for receptor cross-communication in which activation of a GPCR by a receptor tyrosine kinase is critical for cell motility. Our observations might also clarify the role of
EDG-1
in vascular maturation and angiogenesis.
...
PMID:The sphingosine-1-phosphate receptor EDG-1 is essential for platelet-derived growth factor-induced cell motility. 1170 84
