Cell and Tissue Research

, Volume 347, Issue 1, pp 11–20

Non-Smad signaling pathways

  • Yabing Mu
  • Shyam Kumar Gudey
  • Maréne Landström
Review

Abstract

Transforming growth factor-beta (TGFβ) is a key regulator of cell fate during embryogenesis and has also emerged as a potent driver of the epithelial-mesenchymal transition during tumor progression. TGFβ signals are transduced by transmembrane type I and type II serine/threonine kinase receptors (TβRI and TβRII, respectively). The activated TβR complex phosphorylates Smad2 and Smad3, converting them into transcriptional regulators that complex with Smad4. TGFβ also uses non-Smad signaling pathways such as the p38 and Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways to convey its signals. Ubiquitin ligase tumor necrosis factor (TNF)-receptor-associated factor 6 (TRAF6) and TGFβ-associated kinase 1 (TAK1) have recently been shown to be crucial for the activation of the p38 and JNK MAPK pathways. Other TGFβ-induced non-Smad signaling pathways include the phosphoinositide 3-kinase-Akt-mTOR pathway, the small GTPases Rho, Rac, and Cdc42, and the Ras-Erk-MAPK pathway. Signals induced by TGFβ are tightly regulated and specified by post-translational modifications of the signaling components, since they dictate the subcellular localization, activity, and duration of the signal. In this review, we discuss recent findings in the field of TGFβ-induced responses by non-Smad signaling pathways.

Keywords

Non-Smads Smads TAK1 TGFβ TRAF6 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Yabing Mu
    • 1
    • 2
  • Shyam Kumar Gudey
    • 1
  • Maréne Landström
    • 1
    • 2
  1. 1.Medical BiosciencesUmeå UniversityUmeåSweden
  2. 2.Ludwig Institute for Cancer ResearchUppsala UniversityUppsalaSweden

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