Phytosphingosine-1-phosphate stimulates chemotactic migration of L2071 mouse fibroblasts via pertussis toxin-sensitive G-proteins.
Phytosphingosine-1-phosphate (PhS1P) was found to stimulate an intracellular calcium increase via phospholipase C but not pertussis toxin (PTX)-sensitive G-proteins in L2071 mouse fibroblasts. PhS1P also activated ERK and p38 kinase, and these activations by PhS1P were inhibited by PTX. Moreover, PhS1P stimulated the chemotactic migration of L2071 cells via PTX-sensitive Gi protein(s). In addition, the PhS1P-induced chemotactic migration of L2071 cells was also dramatically inhibited by LY294002 and SB203580 (inhibitors of phosphoinositide 3-kinase and p38 kinase, respectively). L2071 cells are known to express four S1P receptors, i.e., S1P1, S1P2, S1P3, and S1P4, and pretreatment with an S1P1 and S1P3 antagonist (VPC 23019) did not affect on PhS1P-induced chemotaxis. This study demonstrates that PhS1P stimulates at least two different signaling cascades, one is a PTX-insensitive but phospholipase C dependent intracellular calcium increase, and the other is a PTX-sensitive chemotactic migration mediated by phosphoinositide 3-kinase and p38 kinase.
Kim
Mi-Kyoung
MK
Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University, Busan 602-714, Korea.
Park
Kyoung Sun
KS
Lee
Hyuck
H
Kim
Young Dae
YD
Yun
Jeanho
J
Bae
Yoe-Sik
YS
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D004963:Estrenes / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D037342:Pertussis Toxin / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004963:Estrenes; D011760:Pyrrolidinones; D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; C117422:phytosphingosine-1-phosphate; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; D013110:Sphingosine