Nucleocytoplasmic shuttling of Smad proteins

Cell Res. 2009 Jan;19(1):36-46. doi: 10.1038/cr.2008.325.

Abstract

Nuclear accumulation of active Smad complexes is crucial for transduction of transforming growth factor beta (TGF-beta)-superfamily signals from transmembrane receptors into the nucleus. It is now clear that the nucleocytoplasmic distributions of Smads, in both the absence and the presence of a TGF-beta-superfamily signal, are not static, but instead the Smads are continuously shuttling between the nucleus and the cytoplasm in both conditions. This article presents the evidence for continuous nucleocytoplasmic shuttling of Smads. It then reviews different mechanisms that have been proposed to mediate Smad nuclear import and export, and discusses how the Smad steady-state distributions in the absence and the presence of a TGF-beta-superfamily signal are established. Finally, the biological relevance of continuous nucleocytoplasmic shuttling for signaling by TGF-beta superfamily members is discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Nucleus / metabolism*
  • Cytoplasm / metabolism
  • Karyopherins / metabolism
  • Receptors, Transforming Growth Factor beta / physiology*
  • Signal Transduction
  • Smad Proteins / metabolism*
  • Smad Proteins / physiology
  • Transforming Growth Factor beta / physiology*

Substances

  • Karyopherins
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • Transforming Growth Factor beta