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Non-Smad signaling pathways

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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.

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Acknowledgements

We thank Carl-Henrik Heldin for comments on our review, and we are grateful to all the past and present members of the apoptotic signaling group for their contributions to the scientific endeavors of our laboratory.

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Authors and Affiliations

  1. Medical Biosciences, Umeå University, SE-901 85, Umeå, Sweden

    Yabing Mu, Shyam Kumar Gudey & Maréne Landström

  2. Ludwig Institute for Cancer Research, Uppsala University, SE-751 24, Uppsala, Sweden

    Yabing Mu & Maréne Landström

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  1. Yabing Mu
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  2. Shyam Kumar Gudey
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Correspondence to Maréne Landström.

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The authors acknowledge funding by the Ludwig Institute for Cancer Research, the Swedish Cancer Society, the Swedish Research Council, Umeå University, ALF, and Ragnar Söderbergs Stiftelser.

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Mu, Y., Gudey, S.K. & Landström, M. Non-Smad signaling pathways. Cell Tissue Res 347, 11–20 (2012). https://doi.org/10.1007/s00441-011-1201-y

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