Involvement of protein kinase C and Rho GTPase in the nuclear signalling pathway by transforming growth factor-β1 in rat-2 fibroblast cells

The transforming growth factor (TGF)-β signal-transduction cascade from the cell membrane to the nuclear target is poorly characterised. Here we report that treatment with TGF-β1 induces the levels of endogenous c-fos mRNA in Rat-2 fibroblast cells. In addition, by transient transfection analysis, TGF-β1 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-β1. To understand the signalling cascade by which TGF-β1 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-β1, implying the possible roles of PKC and RhoA GTPase in TGF-β1-induced signalling to c-fos SRE. Copyright (C) 1998 Elsevier Science Inc.