J Neurochem 2001,
PMID: 11238734
Abounader, R; Ranganathan, S; Kim, B Y; Nichols, C; Laterra, J
Scatter factor/hepatocyte growth factor (SF/HGF) and its tyrosine kinase receptor c-met are developmentally expressed, neuroprotective, and tumorigenic within the CNS. In the present study SF/HGF is shown to induce the expression of c-met in two human glioblastoma cell lines, U-373 MG and T98G, and the signaling pathways involved in this induction are dissected. SF/HGF activated mitogen-activated protein kinase (MAPK) and inhibition of either Ras or MAPK-kinase completely inhibited SF/HGF-mediated c-met induction. Inhibition of phospholipase-C (PLC) did not affect c-met induction in either cell line. Inhibition of phosphoinositide 3-kinase (PI3-kinase) substantially reduced c-met induction by SF/HGF in T98G cells but had no effect in U-373 MG cells. Protein kinase C (PKC) inhibition reduced c-met induction in T98G cells but not in U-373 MG cells. SF/HGF induced the expression of c-fos and c-jun mRNA and increased the levels of AP-1 transcription factor in both cells lines as determined by AP-1-luciferase reporter expression. Transfection of either cell line with TAM-67, a dominant negative for the jun transactivation domain, completely inhibited AP-1 and c-met induction by SF/HGF. These results support a model of c-met induction by SF/HGF in human glioma cells that uniformly involves Ras, MAPK, and AP-1 and additionally involves PI3-kinase and PKC in some cell lines.
Diseases/Pathways annotated by Medline MESH: Glioblastoma
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Text Mining Data
mitogen activated protein kinase ⊣ SF/HGF: "
SF/HGF activated
mitogen activated protein kinase ( MAPK ) and inhibition of either Ras or MAPK-kinase completely
inhibited SF/HGF mediated c-met induction
"
transcription factor → SF/HGF: "
SF/HGF induced the expression of c-fos and c-jun mRNA and increased the levels of AP-1 transcription factor in both cells lines as determined by AP-1-luciferase reporter expression
"
MAPK — PI3-kinase: "
These results support a model of c-met induction by SF/HGF in human glioma cells that uniformly involves Ras, MAPK , and AP-1 and additionally involves PI3-kinase and PKC in some cell lines
"
AP-1 — PI3-kinase: "
These results support a model of c-met induction by SF/HGF in human glioma cells that uniformly involves Ras, MAPK, and AP-1 and additionally involves PI3-kinase and PKC in some cell lines
"
Manually curated Databases
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OpenBEL Selventa BEL large corpus:
O/- complex ()
→
HGF
(increases, HGF Activity)
Evidence: SF/HGF induced the expression of c-fos and c-jun mRNA and increased the levels of AP-1 transcription factor in both cells lines as determined by AP-1-luciferase reporter expression. Transfection of either cell line with TAM-67, a dominant negative for the jun transactivation domain, completely inhibited AP-1 and c-met induction by SF/HGF.