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Signal transduction

Feedback from inhibitory SMADs

Nature volume 389, pages 549–551 (1997)Cite this article

Members of the transforming growth factor-β (TGF-β) superfamily are implicated in biological processes ranging from inhibition of cell proliferation in somatic tissues, to specification of cell fate during embryogenesis. Over the past two years, understanding of the intracellular pathways by which TGF-β signals are mediated has been spurred by studies of the SMAD family of signal transducers1. Discovered through genetic screens in Drosophila melanogaster and Caenorhabditis elegans, the biochemistry and cell biology of vertebrate SMADs has implicated them as regulators of the cell-type specific transcriptional responses that are induced by TGF-β ligands. Now, papers in this issue by Imamura et al.2, Tsuneizumi et al.3 and Nakao et al.4 (pages 622, 627 and 631), along with the work of Hayashi et al.5 in Cell, expose a new aspect of SMADs — some of them inhibit, rather than mediate, TGF-β signalling. These inhibitory SMADs are, themselves, induced by TGF-β stimulation, suggesting that there is an intracellular negative-feedback loop that regulates TGF-β signals.

Now, Imamura et al.2, Nakao et al.4 and Hayashi et al.5 report that Smad6 and Smad7 inhibit the vertebrate SMAD-based signalling pathway described above. Moreover, Tsuneizumi et al.3 show that, in a homologous signalling pathway in Drosophila, the product of the Daughters against decapentaplegic (Dad) gene is an inhibitory SMAD. Overexpression of these newly discovered SMADs inhibits intracellular signalling by members of the TGF-β superfamily. Smad6 and Smad7 can inhibit both TGF-β and BMP signalling in cultured cells or in frog embryos2,4,5. The Dad gene inhibits patterning by decapentaplegic, a Drosophila BMP homologue, in the Drosophila imaginal wing disk3. Like Smad4, these inhibitory SMADs lack the carboxy-terminal phosphorylation site that is found in each of the pathwayspecific SMADs. But unlike Smad4, Smads 6 and 7 do interact with type I receptors — and they probably interact more stably than do the pathway-specific SMADs. Presumably, this is because Smad6 and Smad7 lack the carboxy-terminal phosphorylation site, so they are not phosphorylated and released from activated receptor kinase.

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Figure 1: SMADs involved in the transmission and inhibition of transforming growth factor-β (TGF-β) superfamily signals.

References

  1. Massagué, J., Hata, A. & Liu, F. Trends Cell Biol. 7, 187–192 (1997).

    Google Scholar 

  2. Imamura, T. et al. Nature 389, 622–626 (1997).

    Article  ADS  CAS  Google Scholar 

  3. Tsuneizumi, K. et al. Nature 389, 627–631 (1997).

    Article  ADS  CAS  Google Scholar 

  4. Nakao, A. et al. Nature 389, 631–635 (1997).

    Article  ADS  CAS  Google Scholar 

  5. Hayashi, H. et al. Cell 89, 1165–1174 (1997).

    Google Scholar 

  6. Topper, J. N. et al. Proc. Natl Acad. Sci. USA 94, 9314–9319 (1997).

    Google Scholar 

  7. Alevizopoulos, A. & Mermod, N. Bioessays 19, 581–591 (1997).

    Google Scholar 

  8. Neumann, C. & Cohen, S. Bioessays 19, 721–729 (1997).

    Google Scholar 

  9. Chen, X. et al. Nature 389, 85–89 (1997).

    Article  ADS  CAS  Google Scholar 

  10. Kim, J., Johnson, K., Chen, H. J., Carroll, S. & Laughon, A. Nature 388, 304–308 (1997).

    Article  ADS  CAS  Google Scholar 

  11. Raftery, L. A., Twombly, V., Wharton, K. & Gelbart, W. Genetics 139, 241–254 (1995).

    Google Scholar 

Download references

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  1. the Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Malcolm Whitman

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Whitman, M. Feedback from inhibitory SMADs. Nature 389, 549–551 (1997). https://doi.org/10.1038/39202

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