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. 2012 Jul 12;8(7):964–978. doi: 10.7150/ijbs.4564

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© Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.

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TGF-β signaling pathway. TGF-β ligand is secreted as a latent precursor protein, bound to LAP. Activation of TGF-β involves cleavage of LAP from the ligand, which then binds to the type II receptor, and drives hetero-tetramerization with the type I receptor. The canonical signaling pathway involves phosphorylation of R-Smads (mainly Smad2 and Smad3) by activated TβRI. Phosphorylated R-Smads form a complex with the Co-Smad (Smad4), which translocates into the nucleus to bind gene promoters and activate expression of target genes. There are several non-canonical (non-Smad) signaling pathways, whereby TGF-β signals through the TGF-β receptors to activate TGF-β activated kinase 1 (Tak1), Ras and PI3K as well as other pathways.