Hepatocyte growth factor induces delayed STAT3 phosphorylation through interleukin-6 expression

Bok Soon Lee, Minseon Park, Hyun Young Cha, Jae Ho Lee

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Met receptor tyrosine kinase mediates pleiotropic cellular responses following its activation by hepatocyte growth factor or scatter factor (HGF/SF). STAT3 was reported to be one of direct downstream molecules in HGF/SF-Met signaling. In the present study, however, we observed that Tyr705 of STAT3 was phosphorylated from 2 h or 6 h in NIH3T3 and Chang liver cells, respectively, after HGF/SF treatment. Blocking of the phosphorylation by cycloheximide or actinomycin D and the rapid STAT3 phosphorylation with the conditioned medium from HGF/SF-treated NIH3T3 cells suggested that a newly synthesized secretory protein was responsible for the delayed STAT3 phosphorylation. Among the known mediators to induce STAT3 phosphorylation, interleukin-6 (IL-6) mRNA and protein were induced by HGF/SF, and the released IL-6 was accumulated in the conditioned medium after HGF/SF treatment. Furthermore, the neutralizing IL-6 antibody abolished the STAT3 phosphorylation. Treatment with LY294002, a PI3 kinase inhibitor, but not with other signal inhibitors, resulted in the loss of delayed STAT3 phosphorylation by HGF/SF, showing the involvement of PI3 kinase pathway. Collectively, these results demonstrate that HGF/SF-Met signal cascade stimulates IL-6 production via PI3 kinase pathway, leading to STAT3 phosphorylation as a secondary effect.

Original languageEnglish (US)
Pages (from-to)419-427
Number of pages9
JournalCellular Signalling
Volume21
Issue number3
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

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Hepatocyte Growth Factor
Interleukin-6
Phosphorylation
Phosphatidylinositol 3-Kinases
Conditioned Culture Medium
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Receptor Protein-Tyrosine Kinases
Dactinomycin
Cycloheximide

Keywords

  • HGF/SF
  • Interleukin-6
  • Met
  • PI3K
  • STAT3

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hepatocyte growth factor induces delayed STAT3 phosphorylation through interleukin-6 expression. / Lee, Bok Soon; Park, Minseon; Cha, Hyun Young; Lee, Jae Ho.

In: Cellular Signalling, Vol. 21, No. 3, 01.03.2009, p. 419-427.

Research output: Contribution to journalArticle

Lee, Bok Soon ; Park, Minseon ; Cha, Hyun Young ; Lee, Jae Ho. / Hepatocyte growth factor induces delayed STAT3 phosphorylation through interleukin-6 expression. In: Cellular Signalling. 2009 ; Vol. 21, No. 3. pp. 419-427.
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