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 journalArticlepeer-review

5 Scopus citations


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
Issue number3
StatePublished - Mar 2009
Externally publishedYes


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

ASJC Scopus subject areas

  • Cell Biology


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