Sphingosine 1-phosphate induces expression of early growth response-1 and fibroblast growth factor-2 through mechanism involving extracellular signal-regulated kinase in astroglial cells.
In rat type I astrocytes and C6 glioma cells, sphingosine 1-phosphate (S1P) clearly induced the expression of fibroblast growth factor-2 (FGF-2) mRNA to an extent comparable to that achieved by platelet-derived growth factor (PDGF) and endothelin. In C6 cells, Western blotting showed that S1P also induced expression of early growth response-1 (Egr-1), one of the immediate early gene products and an essential transcriptional factor for FGF-2 expression. On the other hand, sphingosine, a substrate for sphingosine kinase which forms intracellular S1P, was a very weak activator for the expression of either FGF-2 or Egr-1. The S1P-induced Egr-1 expression was partially inhibited by treatment of the cells with either calphostin C, an inhibitor of protein kinase C (PKC), or pertussis toxin (PTX), and completely inhibited by the combination of these agents. Essentially, the same inhibitory pattern by these agents has been observed for S1P-induced extracellular signal-regulated kinase (ERK) activation. The S1P-induced expression of Egr-1 was also completely inhibited in association with complete inhibition of ERK by PD 98059, an ERK kinase inhibitor. Thus, the S1P-induced activation of the Egr-1/FGF-2 system may be mediated through ERK activation, which may involve at least two signaling pathways, i.e., a PTX-sensitive G-protein-dependent pathway and a PKC-dependent pathway.
Sato
K
K
Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Japan. kosato@akagi.sb.gunma-u.ac.jp
Ishikawa
K
K
Ui
M
M
Okajima
F
F
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000187:drug effects*; D051766:Early Growth Response Protein 1; D016232:Endothelins / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005419:Flavonoids / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D017874:Immediate-Early Proteins; D008246:Lysophospholipids; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D037342:Pertussis Toxin; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D016232:Endothelins; D005419:Flavonoids; D017874:Immediate-Early Proteins; D008246:Lysophospholipids; D009281:Naphthalenes; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D014157:Transcription Factors; D010566:Virulence Factors, Bordetella; D016222:Fibroblast Growth Factor 2; C060506:sphingosine 1-phosphate; D037342:Pertussis Toxin; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; C058819:calphostin C; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one