Smad proteins, the mammalian homologs of the Drosophila mothers against decapentaplegic (Mad), have been implicated as downstream effectors of GFbeta/BMP signaling. Smad1 (also designated Madr1 or JV4-1) and Smad5 are effectors of BMP-2 and BMP-4 function, while Smad2 (also designated Madr2 or JV18-1) and Smad3 are involved in TGFbeta and activin-mediated growth modulation. Smad4 (also designated DPC4) has been shown to mediate all of the above activities through interaction with various Smad family members. Smad6 and Smad7 regulate the response to activin/TGFbeta signaling by interfering with TGFbeta-mediated phosphorylation of other Smad proteins.
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