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, whic h 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-b eta like receptors, where they become phosphorylated and translocate t o the nucleus. Once in the nucleus they may function as transcriptiona l 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 tha t it is capable of nuclear translocation, in Drosophila S2 cells, when the dpp pathway is stimulated. To prove the functional conservation o f receptor/Smad interactions, we used the mouse BMP type I receptor AL K6 to stimulate the pathway and found that it is capable of sending MA D to the nucleus. These results show that cytoplasmic localization wit h translocation to the nucleus upon stimulation is a feature of the Sm ads that is conserved through evolution. (C) 1997 Academic Press.