Back to Search
Start Over
Hepatocyte Growth Factor Signal Coupling to Various Transcription Factors Depends on Triggering of Met Receptor and Protein Kinase Transducers in Human Hepatoma Cells HepG2
- Source :
- Experimental Cell Research. 256:272-281
- Publication Year :
- 2000
- Publisher :
- Elsevier BV, 2000.
-
Abstract
- Hepatocyte growth factor (HGF) regulates a wide variety of biological activities by binding to the tyrosine kinase receptor Met. In HGF-treated hepatocarcinoma cells, we observed a biphasic activation of AP-1 and AP-2 transcription factors. For NF-kappaB complex the p50-p50 homodimer was activated before the p50-p65 heterodimer, and c-Myc/Max DNA-binding activity increased thereafter. Since these transcription factors are responders to mitogenic stimulation through protein kinase transducers, we tested the effects of inhibitors of these enzymes on the DNA binding after HGF treatment. Inhibition of protein kinase C (PKC) with H7 strikingly activated NF-kappaB above the values observed after HGF alone. Under this inhibitory condition, Met tyrosine phosphorylation was elevated as though the phosphorylation-dependent activity of the receptor was partially blocked by activation of PKC due to HGF. NF-kappaB DNA binding seems to be related to Met triggering by HGF since it was largely prevented by genistein treatment, which blocks receptor activity. Phosphatidylinositol 3-kinase seems to be involved in AP-1 binding activity stimulated by HGF. It is noteworthy that Met is responsive to HGF stimulating postreceptor signaling, which converges on the activation of transcription factors acting coordinately to regulate target gene expression.
- Subjects :
- Carcinoma, Hepatocellular
Basic helix-loop-helix leucine zipper transcription factors
Receptor tyrosine kinase
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Tumor Cells, Cultured
medicine
Humans
Phosphotyrosine
Protein kinase A
Transcription factor
Protein Kinase C
Protein kinase C
biology
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Hepatocyte Growth Factor
Liver Neoplasms
NF-kappa B
Tyrosine phosphorylation
Cell Biology
Proto-Oncogene Proteins c-met
Molecular biology
DNA-Binding Proteins
Transcription Factor AP-1
Basic-Leucine Zipper Transcription Factors
Transcription Factor AP-2
chemistry
biology.protein
Hepatocyte growth factor
Signal transduction
Dimerization
Signal Transduction
Transcription Factors
medicine.drug
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 256
- Database :
- OpenAIRE
- Journal :
- Experimental Cell Research
- Accession number :
- edsair.doi.dedup.....28e9a78229d63ebc3ca1e882eb94f1af