Members of the Smad family of signal transduction molecules are components of a critical intracellular pathway that transmit TGF-β signals from the cell surface into the nucleus. Smad1 and Smad5 are effectors of BMP-2 and BMP-4 function, while Smad2 and Smad3 are involved in TGF-β and Activin-mediated growth modulation. Smad4 has been shown to mediate all of the above activities through interaction with various Smad family members. The phosphorylated receptor-regulated Smad issociates from the receptor and forms a heteromeric complex with the co-Smad (Smad4), allowing translocation of the complex to the nucleus. Once in the nucleus, Smads can target a variety of DNA binding proteins to regulate transcriptional responses.
