Non-Smad pathways in TGF-beta signaling

Cell Res. 2009 Jan;19(1):128-39. doi: 10.1038/cr.2008.328.


Transforming growth factor-beta utilizes a multitude of intracellular signaling pathways in addition to Smads to regulate a wide array of cellular functions. These non-canonical, non-Smad pathways are activated directly by ligand-occupied receptors to reinforce, attenuate, or otherwise modulate downstream cellular responses. These non-Smad pathways include various branches of MAP kinase pathways, Rho-like GTPase signaling pathways, and phosphatidylinositol-3-kinase/AKT pathways. This review focuses on recent advances in the understanding of the molecular and biochemical mechanisms of non-Smad pathways. In addition, functions of these non-Smad pathways are also discussed.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • MAP Kinase Signaling System
  • Oncogene Protein v-akt / physiology
  • Phosphatidylinositol 3-Kinases / physiology
  • Receptors, Transforming Growth Factor beta / physiology*
  • Signal Transduction*
  • Transforming Growth Factor beta / physiology*
  • rho GTP-Binding Proteins / physiology


  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Phosphatidylinositol 3-Kinases
  • Oncogene Protein v-akt
  • rho GTP-Binding Proteins