Cell and Tissue Research

, Volume 347, Issue 1, pp 11–20

Non-Smad signaling pathways

Authors

  • Yabing Mu
    • Medical BiosciencesUmeå University
    • Ludwig Institute for Cancer ResearchUppsala University
  • Shyam Kumar Gudey
    • Medical BiosciencesUmeå University
    • Medical BiosciencesUmeå University
    • Ludwig Institute for Cancer ResearchUppsala University
Review

DOI: 10.1007/s00441-011-1201-y

Cite this article as:
Mu, Y., Gudey, S.K. & Landström, M. Cell Tissue Res (2012) 347: 11. doi:10.1007/s00441-011-1201-y

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-SmadsSmadsTAK1TGFβTRAF6

Copyright information

© Springer-Verlag 2011