TGF-1 signaling. At the cell surface, TGF-1 binds a complex of transmembrane receptor serine/threonine kinases types I and II (TGF-RI and TGF-RII) and induces transphosphorylation of the the type I receptor by the type II receptor kinases. The activated type I receptor phosphorylates Smad2 and Smad3, which then form a complex with a common Smad4. Activated Smad complexes translocate to the nucleus and function as transcription factors. Activation of R-Smads by type I receptor kinases is inhibited by Smad6 or Smad7. R-Smads and Smad4 shuttle between nucleus and cytoplasm.
