Exp Mol Med.  2007 Apr;39(2):185-194.

Phytosphingosine-1-phosphate stimulates chemotactic migration of L2071 mouse fibroblasts via pertussis toxin-sensitive G-proteins

• Kim MK
• Park KS
• Lee H
• Kim YD
• Yun J
• Bae YS

Abstract

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.

Keyword

calcium signaling; chemotaxis; fibroblasts; GTP-binding proteins; pertussis toxin; phytosphingosine-1-phosphate

MeSH Terms

1-Phosphatidylinositol 3-Kinase/metabolism
Animals
Calcium Signaling/drug effects
Chemotaxis/*drug effects
Estrenes/pharmacology
Extracellular Signal-Regulated MAP Kinases/metabolism
Fibroblasts/*cytology/*drug effects
GTP-Binding Proteins/*metabolism
Gene Expression Regulation/drug effects
Humans
Mice
Pertussis Toxin/*pharmacology
Phosphorylation/drug effects
Pyrrolidinones/pharmacology
RNA, Messenger/genetics/metabolism
Receptors, Lysosphingolipid/genetics/metabolism
Sphingosine/*analogs & derivatives/pharmacology
p38 Mitogen-Activated Protein Kinases/metabolism