Inhibition of transforming growth factor-β/SMAD signalling by the interferon-γ/STAT pathway Journal Article
| Authors: | Ulloa, L.; Doody, J.; Massagué, J. |
| Article Title: | Inhibition of transforming growth factor-β/SMAD signalling by the interferon-γ/STAT pathway |
| Abstract: | Transforming growth factor-β (TGF-β) and interferon-γ (IFN-γ) have opposite effects on diverse cellular functions1-5, but the basis for this antagonism is not known6. TGF-β signals through a receptor serine kinase that phosphorylates and activates the transcription factors Smads 2 and 3 (refs 7, 8), whereas the IFN-γ receptor and its associated protein tyrosine kinase Jak1 mediate phosphorylation and activation of the transcription factor Stat1 (refs 6, 9, 10). Here we present a basis for the integration of TGF-β and IFN-γ signals. IFN-γ inhibits the TGF β-induced phosphorylation of Smad3 and its attendant event:, namely, the association of Smad3 with Smad4, the accumulation of Smad3 in the nucleus, and the activation of TGFβ- responsive genes. Acting through Jak1 and Stat1, IFN-γ induces the expression of Smad7, an antagonistic SMAD11,12, which prevents the interaction of Smad3 with the TGF-β receptor. The results indicate a mechanism of transmodulation between the STAT and SMAD signal-transduction pathways. |
| Keywords: | signal transduction; protein phosphorylation; dna-binding proteins; nonhuman; animal cell; stat1 protein; smad3 protein; smad7 protein; transforming growth factor beta; protein protein interaction; cell line; protein tyrosine kinase; phosphorylation; gene expression regulation; molecular sequence data; genetic transfection; gamma interferon; cell culture; receptors, transforming growth factor beta; protein-tyrosine kinases; trans-activators; cell nucleus; luciferases; receptor binding; janus kinase 1; interferon type ii; stat1 transcription factor; humans; priority journal; article |
| Journal Title: | Nature |
| Volume: | 397 |
| Issue: | 6721 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1999-02-25 |
| Start Page: | 710 |
| End Page: | 713 |
| Language: | English |
| DOI: | 10.1038/17826 |
| PUBMED: | 10067896 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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