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. TGFβ type I receptor mediates phosphorylation of Smad2 (also designated Madr2 or JV18-1) at the C-terminal Ser 465 and Ser 467 residues, and phosphoryla-tion of Smad3 at the C-terminal Ser 423 and Ser 425 residues in an obligate order. Upon phosphorylation and activation by the active TGFβ receptor complex, Smad2 and Smad3 homo-oligomerize or hetero-oligomerize with Smad4, and translocate into the nucleus.
