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. Author manuscript; available in PMC: 2007 Oct 29.
Published in final edited form as: Cells Tissues Organs. 2007;185(1-3):131–145. doi: 10.1159/000101314

Fig. 3.

Fig. 3

TGF-β signaling. Smad-dependent: TGF-β ligand binds to receptors I and II at the cell surface. After phosphorylation of TGFβRI with TGFβRII kinase, the receptor forms a complex with Smad2 or Smad3. Smad2 (or Smad3) is phosphorylated and then complexes with Smad4 to enter the nucleus and activate EMT-related gene. Smad-independent: TGF-β can also signal through the MAPK such as ERK and p38 to activate several transcription factors that induce target gene expression as well as via the PI3K and RhoA pathways, which have been shown to be key mediators of EMT. MAPK can also activate Jagged1, which in turn signals via NOTCH to activate bHLH-related transcription factors. At the end, these activated transcription factors (the ‘X’ transcription factors) bind to appropriate binding sites of the EMT genes and either alone (−) or with (+) Smads bound at Smad binding elements (SBE) can regulate EMT-related genes. These activities can be regulated by corepressors and coactivators such as p300/CBP or Ski/SnoN (green arrows are the flow of the signals and red arrows are the repressors).