Involvement of protein kinase C and rho GTPase in the nuclear signalling pathway by transforming growth factor-beta1 in rat-2 fibroblast cells.
The transforming growth factor (TGF)-beta signal-transduction cascade from the cell membrane to the nuclear target is poorly characterised. Here we report that treatment with TGF-beta1 induces the levels of endogenous c-fos mRNA in Rat-2 fibroblast cells. In addition, by transient transfection analysis, TGF-beta1 was shown to stimulate c-fos serum response element (SRE)-driven reporter gene activity in a dose- and time-dependent manner, suggesting that SRE is one of the nuclear targets of TGF-beta1. To understand the signalling cascade by which TGF-beta1 mediates the transactivation of c-fos SRE, cells were either pre-treated with various inhibitors or co-transfected with expression plasmids encoding inhibitory proteins for Rho GTPase together with the SRE-luciferase reporter gene. Our results showed that an inhibition of protein kinase C (PKC) or RhoA selectively repressed the stimulation of c-fos SRE by TGF-beta1, implying the possible roles of PKC and RhoA GTPase in TGF-beta1-induced signalling to c-fos SRE.
Choi
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Institute of Environment and Life Science, Hallym University, Chun-Cheon, South Korea.
Choi
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Kim
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Kim
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D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1; D020742:rhoA GTP-Binding Protein
D004268:DNA-Binding Proteins; C494114:Elk1 protein, rat; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D050807:ets-Domain Protein Elk-1; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein