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Tob proteins enhance inhibitory Smad-receptor interactions to repress BMP signaling

Yutaka Yoshida1, Andreas von Bubnoff, Naoko Ikematsu

  • 1Department of Oncology, The Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan.

Mechanisms of Development
|June 5, 2003
PubMed

Insights

Tob proteins inhibit bone morphogenetic protein (BMP) signaling by enhancing the function of inhibitory Smads. This interaction occurs at the cell membrane and is crucial for regulating BMP pathways in both embryonic and adult cells.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Developmental Biology

Background:

  • Tob proteins are known inhibitors of bone morphogenetic protein (BMP) signaling.
  • Tob proteins interact with receptor-regulated Smads in osteoblasts.

Purpose of the Study:

  • To investigate the interaction of Tob proteins with inhibitory Smads (Smad6 and Smad7).
  • To elucidate the role of Tob and its homolog Tob2 in BMP signaling regulation in vivo and in vitro.

Main Methods:

  • Yeast two-hybrid screening to identify interacting proteins.
  • Co-localization studies at the plasma membrane.
  • Xenopus embryo assays to assess functional cooperation.
  • Mammalian cell culture experiments.

Main Results:

  • Smad6 was identified as a Tob-interacting protein via yeast two-hybrid screening.
  • Tob co-localizes with Smad6 at the plasma membrane, enhancing Smad6 interaction with BMP type I receptors.
  • Xenopus Tob2 cooperates with Smad6 to induce secondary axes in embryos.
  • Tob and Tob2, in conjunction with Smad6, inhibit endogenous BMP signaling in both Xenopus and mammalian cells.

Conclusions:

  • Tob proteins inhibit BMP signaling by facilitating the functions of inhibitory Smads, specifically Smad6.
  • This mechanism involves interaction at the plasma membrane and is conserved across species and cell types.
  • The findings provide in vitro and in vivo evidence for Tob's role in regulating BMP signaling through inhibitory Smad pathways.

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