PMID- 19071214
OWN - NLM
STAT- MEDLINE
DCOM- 20090420
LR  - 20191210
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 21
IP  - 3
DP  - 2009 Mar
TI  - Hepatocyte growth factor induces delayed STAT3 phosphorylation through 
      interleukin-6 expression.
PG  - 419-27
LID - 10.1016/j.cellsig.2008.11.010 [doi]
AB  - 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.
FAU - Lee, Bok-Soon
AU  - Lee BS
AD  - Department of Biochemistry and Molecular Biology, Ajou University Medical School, 
      5 Wonchon-Dong, Yeongtong-Gu, Suwon 443-721, South Korea.
FAU - Park, Minseon
AU  - Park M
FAU - Cha, Hyun-Young
AU  - Cha HY
FAU - Lee, Jae-Ho
AU  - Lee JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081130
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-6)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - Culture Media, Conditioned/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibroblasts/drug effects/metabolism
MH  - Hepatocyte Growth Factor/*metabolism/pharmacology
MH  - Hepatocytes/drug effects/metabolism
MH  - Interleukin-6/genetics/*metabolism
MH  - Mice
MH  - NIH 3T3 Cells
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation/drug effects
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - RNA, Messenger/drug effects/metabolism
MH  - STAT3 Transcription Factor/drug effects/*metabolism
MH  - Signal Transduction/drug effects/*physiology
EDAT- 2008/12/17 09:00
MHDA- 2009/04/21 09:00
CRDT- 2008/12/17 09:00
PHST- 2008/08/09 00:00 [received]
PHST- 2008/11/13 00:00 [revised]
PHST- 2008/11/15 00:00 [accepted]
PHST- 2008/12/17 09:00 [entrez]
PHST- 2008/12/17 09:00 [pubmed]
PHST- 2009/04/21 09:00 [medline]
AID - S0898-6568(08)00343-4 [pii]
AID - 10.1016/j.cellsig.2008.11.010 [doi]
PST - ppublish
SO  - Cell Signal. 2009 Mar;21(3):419-27. doi: 10.1016/j.cellsig.2008.11.010. Epub 2008 
      Nov 30.