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. 2014 Nov 14;5(1):52. doi: 10.1186/2049-1891-5-52

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© Li; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Canonical and non-canonical TGFβ signaling. In the canonical pathway, TGFβ ligands bind to serine/threonine kinase type II and type I receptors and phosphorylate R-SMADs, which form heteromeric complexes with SMAD4 and translocate into the nucleus to regulate gene transcription. The non-canonical pathway generally refers to the SMAD-independent pathway such as PI3K-AKT, ERK1/2, p38, and JNK pathways. Recent studies have identified an “R-SMAD-dependent but SMAD4-independent” non-canonical pathway that regulates miRNA maturation.