TGF-beta Signaling

The transforming growth factor beta (TGF-Beta) signaling pathway is involved in many cellular processes among which, the regulation of cell growth and differentiation. So, defects in TGF-Beta signaling pathways have been linked to uncontrolled cellular proliferation and carcinogenesis. Briefly, a TGF-Beta superfamily ligand induces the heteromeric complex formation of two serine/threonine kinase receptors, type I and type II TGF-Beta receptors. The type II receptor phosphorylates the type I receptor that, once activated, in turn phosphorylates downstream R-Smad proteins (in particular Smad2 and 3), activating them to transduce the signal to the nucleus with the help of the common partner Smad4 and thus participating in the regulation of target genes expression. Other members of the SMAD family of transcriptional regulators also participate in the regulation of the TGF-Beta signaling pathway. Moreover, other signaling pathways like the MAP kinase-ERK cascade are activated by TGF-Beta signaling.