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Figure 3. Smad signaling. The activated TßR-I kinase phosphorylates the R-Smads, Smad2 and Smad3, which then form heterodimers with the Co-Smad, Smad4. The complex translates to the nucleus and regulates gene transcription by binding directly to DNA via interactions with DNA-binding proteins and/or transcriptional co-activators and co-repressors. The transcription of the I-Smad, Smad7, is induced, and Smad7 exits the nucleus to control the intensity and duration of signaling via a negative feedback mechanism.
