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Post‐translational regulation of TGF‐β receptor and Smad signaling
Author(s) -
Xu Pinglong,
Liu Jianming,
Derynck Rik
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.05.010
Subject(s) - smad , r smad , microbiology and biotechnology , signal transduction , transcription factor , receptor , phosphorylation , smad2 protein , biology , transforming growth factor , chemistry , genetics , gene , tgf alpha , epidermal growth factor
TGF‐β family signaling through Smads is conceptually a simple and linear signaling pathway, driven by sequential phosphorylation, with type II receptors activating type I receptors, which in turn activate R‐Smads. Nevertheless, TGF‐β family proteins induce highly complex programs of gene expression responses that are extensively regulated, and depend on the physiological context of the cells. Regulation of TGF‐β signaling occurs at multiple levels, including TGF‐β activation, formation, activation and destruction of functional TGF‐β receptor complexes, activation and degradation of Smads, and formation of Smad transcription complexes at regulatory gene sequences that cooperate with a diverse set of DNA binding transcription factors and coregulators. Here we discuss recent insights into the roles of post‐translational modifications and molecular interaction networks in the functions of receptors and Smads in TGF‐β signal responses. These layers of regulation demonstrate how a simple signaling system can be coopted to exert exquisitely regulated, complex responses.