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

G Lagna, A Hata, A Hemmati-Brivanlou, J Massagué - Nature, 1996 - nature.com
G Lagna, A Hata, A Hemmati-Brivanlou, J Massagué
Nature, 1996nature.com
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 …
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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