Figure 3

The SMAD signal-transduction pathway as a downstream mediator of TGF-β action. The TGF-β receptor consists of type I and type II subunits that are serine-threonine kinases that signal through the SMAD family of proteins. Binding of TGF-β to its cell-surface receptor type II causes phosphorylation of the type I receptor by type II. The type I receptor is then able to phosphorylate and activate the R-SMAD proteins. Once these SMADs are phosphorylated, they form a complex with the common mediator Co-SMAD 4. This SMAD complex translocates to the nucleus, where the activated SMAD complex recruits other transcription factors (TF) that together activate the expression of target genes mediating the biological effects of TGF-β. Inhibitory SMAD 7 is able to prevent phosphorylation of R-SMADs by forming stable associations with activated type I TGF-β receptors and thus provides negative feedback to the actions of TGF-β.