Drosophila MAD, a member of the Smad family, translocates to the nucleus upon stimulation of the dpp pathway.

Smads are a novel group of proteins which act to mediate signaling by members of the TGF-beta superfamily. Seven vertebrate Smad genes, which fall into three classes, have been reported. Members of the Class I Smads have been shown to bind to the cytoplasmic portion of the TGF-beta like receptors, where they become phosphorylated and translocate to the nucleus. Once in the nucleus they may function as transcriptional activators. We wondered if translocation to the nucleus is a general property of the Smads and whether it was evolutionarily conserved. We examined the subcellular localization of Drosophila MAD and found that it is capable of nuclear translocation, in Drosophila S2 cells, when the dpp pathway is stimulated. To prove the functional conservation of receptor/Smad interactions, we used the mouse BMP type I receptor ALK6 to stimulate the pathway and found that it is capable of sending MAD to the nucleus. These results show that cytoplasmic localization with translocation to the nucleus upon stimulation is a feature of the Smads that is conserved through evolution.