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Role of Smads in TGFβ signaling

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Abstract

Transforming growth factor-β (TGFβ) is the prototype for a large family of pleiotropic factors that signal via heterotetrameric complexes of type I and type II serine/threonine kinase receptors. Important intracellular mediators of TGFβ signaling are members of the Smad family. Smad2 and 3 are activated by C-terminal receptor-mediated phosphorylation, whereafter they form complexes with Smad4 and are translocated to the nucleus where they, in cooperation with other transcription factors, co-activators and co-repressors, regulate the transcription of specific genes. Smads have key roles in exerting TGFβ-induced programs leading to cell growth arrest and epithelial-mesenchymal transition. The activity and stability of Smad molecules are carefully regulated by a plethora of post-translational modifications, including phosphorylation, ubiquitination, sumoylation, acetylation and poly(ADP)-ribosylation. The Smad function has been shown to be perturbed in certain diseases such as cancer.

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Acknowledgments

We are grateful to all past and present members of the TGFβ signaling group for their contributions to the scientific work emanating from our laboratory and to Ingegärd Schiller for assistance with the writing of this review.

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Authors and Affiliations

  1. Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE-751 24, Uppsala, Sweden

    Carl-Henrik Heldin & Aristidis Moustakas

  2. Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23, Uppsala, Sweden

    Aristidis Moustakas

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  1. Carl-Henrik Heldin
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  2. Aristidis Moustakas
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Correspondence to Carl-Henrik Heldin.

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The authors acknowledge funding by the Ludwig Institute for Cancer Research, the Swedish Cancer Society, the Swedish Research Council and the Network of Excellence “ENFIN” under the European Union FP6 program.

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Heldin, CH., Moustakas, A. Role of Smads in TGFβ signaling. Cell Tissue Res 347, 21–36 (2012). https://doi.org/10.1007/s00441-011-1190-x

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