Disease relevance of EDG1

• Taken together, these results indicate that LPA potently activates eNOS in BAEC in a pathway distinct from the EDG-1 receptor, but mediated by a similar receptor-mediated pathway dependent on pertussis toxin-sensitive G proteins and involving activation of the PI3-K/Akt pathway [1].

High impact information on EDG1

• VEGF induces S1P1 receptors in endothelial cells: Implications for cross-talk between sphingolipid and growth factor receptors [2].
• Sphingosine 1-phosphate (S1P) is a platelet-derived sphingolipid that binds to S1P1 (EDG-1) receptors and activates the endothelial isoform of NO synthase (eNOS) [2].
• S1P1 induction by VEGF was attenuated by the tyrosine kinase inhibitor genistein and by the PKC inhibitor calphostin C [2].
• Taken together, these data indicate that VEGF specifically induces expression of S1P1 receptors, associated with enhanced intracellular signaling responses to S1P and the potentiation of S1P-mediated vasorelaxation [2].
• S1P1 up-regulation by VEGF was seen within 30 min of VEGF addition and reached a maximum after 1.5 h [2].

Biological context of EDG1

• Here we show that SPP signals through the EDG-1 receptor to the heterotrimeric G protein G(i), leading to activation of the serine/threonine kinase Akt and phosphorylation of the Akt substrate, endothelial nitric-oxide synthase (eNOS) [3].
• In contrast to the cellular responses elicited by S1P in COS-7 cells, LPA can stimulate the activation of eNOS and Akt independently of EDG-1 receptor transfection [1].

Anatomical context of EDG1

• We suggest that VEGF acts to sensitize the vascular endothelium to the effects of lipid mediators by promoting the induction of S1P1 receptors, representing a potentially important point of cross-talk between receptor-regulated eNOS signaling pathways in the vasculature [2].

References