Sphingosine 1-phosphate activates Erk-1/-2 by transactivating epidermal growth factor receptor in Rat-2 cells

Joo Hee Kim, Jung Hee Kim, Woo Keun Song, Jae-Hong Kim, Jang Soo Chun

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

We investigated a signaling pathway leading to activation of extracellular signal-regulated protein kinase (Erk) 1 and 2 in Rat-2 cells stimulated with sphingosine 1-phosphate (S1P). S1P treatment transiently activated Erk-1/-2 in a dose-dependent manner, and its activation was blocked by pertussis toxin, expression of RasN17, or inhibition of Raf or MEK-1/-2. S1P-induced activation of Erk-1/-2 was also suppressed by the inhibition of epidermal growth factor (EGF) receptor tyrosine kinase with the specific inhibitor AG1478, suggesting that activation of EGF receptor tyrosine kinase was involved in the signaling pathway. S1P-induced Erk-1/-2 activation was enhanced up to 2-fold by inhibiting protein kinase C (PKC) with GF109203X, and PKC inhibition in the absence of S1P treatment also activated Erk-1/-2. The stimulatory effects of Erk-1/-2 activation by PKC inhibition was blocked by treating cells with AG1478, suggesting the involvement of PKC in the regulation of EGF receptor tyrosine kinase activation that leads to Erk-1/-2 activation. Together, these results suggest that S1P activates the EGF receptor through a PKC-dependent pathway that links Ras signaling to the activation of Erk-1/-2 in Rat-2 cells.

Original languageEnglish
Pages (from-to)119-124
Number of pages6
JournalIUBMB Life
Volume50
Issue number2
DOIs
Publication statusPublished - 2000 Jan 1
Externally publishedYes

Keywords

  • EGF receptor
  • Erk-1/-2
  • Protein kinase C
  • Sphingosine 1-phosphate

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Clinical Biochemistry
  • Cell Biology

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