Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Signal transduction

Mad about SMADs

Nature volume 388, pages 28–29 (1997)Cite this article

The transforming growth factor-β (TGF-β) family of signalling molecules can regulate the proliferation of many cell types. Central to TGF-β-mediated signalling in vertebrates are the so-called SMAD proteins and, on pages 82 and 87 of this issue, Hata et al.1 and Shi et al.2 provide our first glimpse of how the structure of these signalling molecules might regulate their function. Moreover, the new results give an insight into the different ways in which mutations in the Smad proteins can disrupt their activity in development and human cancer.

For some time, analysis of signalling by TGF-β concentrated on the activation of serine/threonine kinase receptors at the cell surface. TGF-β binds a type-II receptor kinase, which phosphorylates (and activates) a type-I receptor kinase that then initiates downstream signalling. But the discovery of the MAD-related family of signal transducers has strikingly increased our understanding of intracellular events in the TGF-β pathway. The family now includes the prototypic Drosophila gene, Mothers against dpp (Mad), three genes from Caenorhabditis elegans (sma-2, sma-3 and sma-4) and seven vertebrate members (Smad1-7). The Smad2 and Smad4 proteins are tumour suppressors, and they are involved in TGF-β-mediated signalling3,7.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Smad proteins are involved in TGF-β signalling, and new studies show how the structure of Smads could regulate their function.

References

  1. Hata, A., Lo, R. S., Wotton, D., Lagna, G. & Massagué, J. Nature 388, 82–87 (1997).

    Article  ADS  CAS  Google Scholar 

  2. Shi, Y., Hata, A., Lo, R. S., Massagué, J. & Pavletich, N. P. Nature 388, 87–93 (1997).

    Article  ADS  CAS  Google Scholar 

  3. Hahn, S. A.et al. Science 271, 350–353 (1996).

    Google Scholar 

  4. Eppert, K.et al. Cell 86, 543–552 (1996).

    Google Scholar 

  5. Zhang, Y., Feng, X.-H., Wu, R.-Y. & Derynck, R. Nature 383, 168–172 (1996).

    Article  ADS  CAS  Google Scholar 

  6. Lagna, G., Hata, A., Hemmati-Brivanlou, A. & Massagué, J. Nature 383, 832–836 (1996).

    Article  ADS  CAS  Google Scholar 

  7. Macías-Silva, M.et al. Cell 87, 1215–1224 (1996).

    Google Scholar 

  8. Chen, X., Rubock, M. J. & Whitman, M. Nature 383, 691–696 (1996).

    Article  ADS  CAS  Google Scholar 

  9. Hoodless, P. A.et al. Cell 85, 489–500 (1996).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Program in Developmental Biology and Division of Gastroenterology, The Hospital for Sick Children, Ontario, Toronto, M5G 1X8, Canada

    Jeff Wrans

  2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, M5G 1X8, Ontario, Canada

    Tony Pawson

Authors
  1. Jeff Wrans
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tony Pawson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wrans, J., Pawson, T. Mad about SMADs. Nature 388, 28–29 (1997). https://doi.org/10.1038/40290

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/40290

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing