BACKGROUND: Sphingosine 1-phosphate (Sph-1-P) is a bioactive lipid mediator released from activated platelets, which regulates diverse signal transduction pathways via cell surface receptors. Recent studies have revealed that the seven-transmembrane-spanning receptors, Edg-1, Edg-3, Edg-5, Edg-6 and Edg-8 are specific Sph-1-P receptors. Northern blot analysis has demonstrated that Edg-6 is expressed in lymphocyte-containing tissues such as spleen and lung. Little is known about the molecular mechanisms of Edg-6 functions, probably because of the difficulties in expressing Edg-6 on the cell surface. RESULTS: Here, our studies revealed that N-terminal FLAG-tagged Edg-6 or Edg-6-GFP fusion protein was expressed in the endoplasmic reticulum, but was not expressed on the cell surface. On the other hand, C-terminally tagged Edg-6 or both N-terminally and C-terminally tagged Edg-6 was able to localize to the cell surface. Using these cells, we found that Sph-1-P induced cell migration through cell surface-expressed Edg-6 in a pertussis toxin-sensitive manner. This motility was mediated through the activation of a member of the Rho family of small GTPases, Cdc42. CONCLUSION: These results support a role for Sph-1-P signalling via Edg-6 in the pathways involved in cell motility.
BACKGROUND:Sphingosine 1-phosphate (Sph-1-P) is a bioactive lipid mediator released from activated platelets, which regulates diverse signal transduction pathways via cell surface receptors. Recent studies have revealed that the seven-transmembrane-spanning receptors, Edg-1, Edg-3, Edg-5, Edg-6 and Edg-8 are specific Sph-1-P receptors. Northern blot analysis has demonstrated that Edg-6 is expressed in lymphocyte-containing tissues such as spleen and lung. Little is known about the molecular mechanisms of Edg-6 functions, probably because of the difficulties in expressing Edg-6 on the cell surface. RESULTS: Here, our studies revealed that N-terminal FLAG-tagged Edg-6 or Edg-6-GFP fusion protein was expressed in the endoplasmic reticulum, but was not expressed on the cell surface. On the other hand, C-terminally tagged Edg-6 or both N-terminally and C-terminally tagged Edg-6 was able to localize to the cell surface. Using these cells, we found that Sph-1-P induced cell migration through cell surface-expressed Edg-6 in a pertussis toxin-sensitive manner. This motility was mediated through the activation of a member of the Rho family of small GTPases, Cdc42. CONCLUSION: These results support a role for Sph-1-P signalling via Edg-6 in the pathways involved in cell motility.
Authors: Sonja Balthasar; Johanna Samulin; Hanna Ahlgren; Nina Bergelin; Mathias Lundqvist; Emil C Toescu; Margaret C Eggo; Kid Törnquist Journal: Biochem J Date: 2006-09-15 Impact factor: 3.857
Authors: Mariangela Urbano; Miguel Guerrero; Subash Velaparthi; Melissa Crisp; Peter Chase; Peter Hodder; Marie-Therese Schaeffer; Steven Brown; Hugh Rosen; Edward Roberts Journal: Bioorg Med Chem Lett Date: 2011-09-20 Impact factor: 2.823
Authors: Miguel Guerrero; Mariangela Urbano; Jian Zhao; Melissa Crisp; Peter Chase; Peter Hodder; Marie-Therese Schaeffer; Steven Brown; Hugh Rosen; Edward Roberts Journal: Bioorg Med Chem Lett Date: 2011-11-04 Impact factor: 2.823
Authors: Mariangela Urbano; Miguel Guerrero; Jian Zhao; Subash Velaparthi; Marie-Therese Schaeffer; Steven Brown; Hugh Rosen; Edward Roberts Journal: Bioorg Med Chem Lett Date: 2011-07-13 Impact factor: 2.823
Authors: James Fossetta; Gregory Deno; Waldemar Gonsiorek; Xuedong Fan; Brian Lavey; Pradip Das; Charles Lunn; Paul J Zavodny; Daniel Lundell; R William Hipkin Journal: Br J Pharmacol Date: 2004-06-14 Impact factor: 8.739
Authors: Mor M Naor; Michelle D Walker; James R Van Brocklyn; Gabor Tigyi; Abby L Parrill Journal: J Mol Graph Model Date: 2007-03-14 Impact factor: 2.518