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Partnership between DPC4 and SMAD proteins in TGF-β signalling pathways

Nature volume 383, pages 832–836 (1996)Cite this article

Abstract

THE TGF-β/activin/BMP superfamily of growth factors signals through heteromeric receptor complexes of type I and type II serine/threonine kinase receptors1. The signal originated by TGF-β-like molecules appears to be transduced by a set of evolutionarily conserved proteins known as SMADs, which upon activation directly translocate to the nucleus where they may activate transcription2. Five SMAD proteins have so far been characterized in vertebrates1. These factors are related to the mediator of decapentaplegic (dpp) signalling, mothers against dpp (Mad), in Drosophila3 and to the Sma genes from Caenorhabditis elegans4. Smad1 and Smad2 have been shown to mimic the effects of BMP and activin, respectively, both in Xenopus and in mammalian cells2,5–9, whereas Smad3 (a close homologue of Smad2) and the related protein DPC4, a tumour-suppressor gene product10, mediate TGF-β actions11. We report here that DPC4 is essential for the function of Smadl and Smad2 in pathways that signal mesoderm induction and patterning in Xenopus embryos, as well as antimitogenic and transcriptional responses in breast epithelial cells. DPC4 associates with Smadl in response to BMP and with Smad2 in response to activin or TGF-β. DPC4 is therefore a regulated partner of SMADs that function in different signalling pathways of the TGF-β family.

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Authors and Affiliations

  1. Memorial Sloan-Kettering Cancer Center and Howard Hughes Medical Institute, New York, New York, 10021, USA

    Akiko Hata & Joan Massagué

  2. The Rockefeller University, Laboratory of Molecular Embryology, New York, New York, 10021, USA

    Giorgio Lagna & Ali Hemmati-Brivanlou

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  1. Giorgio Lagna
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  2. Akiko Hata
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  3. Ali Hemmati-Brivanlou
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  4. Joan Massagué
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Lagna, G., Hata, A., Hemmati-Brivanlou, A. et al. Partnership between DPC4 and SMAD proteins in TGF-β signalling pathways. Nature 383, 832–836 (1996). https://doi.org/10.1038/383832a0

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