@article{Ramachandran2018novel-56571,
  year={2018},
  doi={10.7554/eLife.31756},
  title={TGF-β uses a novel mode of receptor activation to phosphorylate SMAD1/5 and induce epithelial-to-mesenchymal transition},
  volume={7},
  journal={eLife},
  author={Ramachandran, Anassuya and Vizán, Pedro and Das, Debipriya and Chakravarty, Probir and Vogt, Janis and Rogers, Katherine W. and Müller, Patrick and Hinck, Andrew P. and Sapkota, Gopal P. and Hill, Caroline S.},
  note={Article Number: e31756}
}

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    <dc:contributor>Vogt, Janis</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-02-15T14:53:53Z</dc:date>
    <dc:creator>Chakravarty, Probir</dc:creator>
    <dc:contributor>Hinck, Andrew P.</dc:contributor>
    <dc:contributor>Vizán, Pedro</dc:contributor>
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    <dc:contributor>Hill, Caroline S.</dc:contributor>
    <dc:creator>Vizán, Pedro</dc:creator>
    <dc:creator>Das, Debipriya</dc:creator>
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    <dc:contributor>Chakravarty, Probir</dc:contributor>
    <dc:creator>Müller, Patrick</dc:creator>
    <dc:contributor>Ramachandran, Anassuya</dc:contributor>
    <dc:contributor>Das, Debipriya</dc:contributor>
    <dc:creator>Hill, Caroline S.</dc:creator>
    <dc:creator>Sapkota, Gopal P.</dc:creator>
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    <dcterms:abstract xml:lang="eng">The best characterized signaling pathway downstream of transforming growth factor β (TGF-β) is through SMAD2 and SMAD3. However, TGF-β also induces phosphorylation of SMAD1 and SMAD5, but the mechanism of this phosphorylation and its functional relevance is not known. Here, we show that TGF-β-induced SMAD1/5 phosphorylation requires members of two classes of type I receptor, TGFBR1 and ACVR1, and establish a new paradigm for receptor activation where TGFBR1 phosphorylates and activates ACVR1, which phosphorylates SMAD1/5. We demonstrate the biological significance of this pathway by showing that approximately a quarter of the TGF-β-induced transcriptome depends on SMAD1/5 signaling, with major early transcriptional targets being the ID genes. Finally, we show that TGF-β-induced epithelial-to-mesenchymal transition requires signaling via both the SMAD3 and SMAD1/5 pathways, with SMAD1/5 signaling being essential to induce ID1. Therefore, combinatorial signaling via both SMAD pathways is essential for the full TGF-β-induced transcriptional program and physiological responses.</dcterms:abstract>
    <dcterms:issued>2018</dcterms:issued>
    <dc:creator>Vogt, Janis</dc:creator>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dc:language>eng</dc:language>
    <dcterms:title>TGF-β uses a novel mode of receptor activation to phosphorylate SMAD1/5 and induce epithelial-to-mesenchymal transition</dcterms:title>
    <dc:contributor>Rogers, Katherine W.</dc:contributor>
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