Cell and Tissue Research

, Volume 347, Issue 1, pp 21–36 | Cite as

Role of Smads in TGFβ signaling

Review

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.

Keywords

TGFβ Receptor Kinase Smad Transcription factor 

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© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Ludwig Institute for Cancer ResearchUppsala UniversityUppsalaSweden
  2. 2.Department of Medical Biochemistry and Microbiology, Science for Life LaboratoryUppsala UniversityUppsalaSweden

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