Cell and Tissue Research

, Volume 347, Issue 1, pp 21-36

First online:

Role of Smads in TGFβ signaling

  • Carl-Henrik HeldinAffiliated withLudwig Institute for Cancer Research, Uppsala University Email author 
  • , Aristidis MoustakasAffiliated withLudwig Institute for Cancer Research, Uppsala UniversityDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University

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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.


TGFβ Receptor Kinase Smad Transcription factor