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. 2018 Apr 30;8:133. doi: 10.3389/fonc.2018.00133

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Copyright © 2018 Verrecchia and Rédini.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The transforming growth factor-β (TGF-β)/Smad signaling pathway. TGF-β dimers bind to two TβRII receptors that induce the assembly of two TβRI and two TβRII receptors into a heterotetrameric complex in which TβRII phosphorylates and activates TβRI. Smad3 (S3) is then phosphorylated and activated by TβRI. Activated S3 dissociates from the Smad anchor for receptor activation protein (SARA) and recruits Smad4 (S4). This protein complex is translocated into the nucleus to regulate target gene expression in association with cofactors (Co-F) and/or p300. Smad7 (S7) recruits E3-ubiquitin ligases (Smurf1 and Smurf2) to activate TRβI, resulting in receptor degradation.