Sphingosine 1-phosphate promotes cell migration through the activation of Cdc42 in Edg-6/S1P4-expressing cells.
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.


CONCLUSIONS
These results support a role for Sph-1-P signalling via Edg-6 in the pathways involved in cell motility.
Kohno
Takayuki
T
Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Nishi 6, Kita 12, Kita-ku, Sapporo 060-0812 Japan.
Matsuyuki
Hirofumi
H
Inagaki
Yuichi
Y
Igarashi
Yasuyuki
Y
D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects*; D006224:Cricetinae; D006801:Humans; D019169:Jurkat Cells; D008246:Lysophospholipids; D051379:Mice; D037342:Pertussis Toxin / Q000494:pharmacology; D011233:Precipitin Tests; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D049312:Receptors, Lysophospholipid; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; C060506:sphingosine 1-phosphate; D037342:Pertussis Toxin; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D013110:Sphingosine