Post-translational regulation of TGF-beta receptor and Smad signaling

作者：Xu Pinglong; Liu Jianming; Derynck Rik^*

来源：FEBS LETTERS, 2012, 586(14): 1871-1884.

DOI：10.1016/j.febslet.2012.05.010

• Transforming growth factor-beta
• Signal transduction
• Smad
• Receptor kinase
• Post-translational modification
• Phosphorylation
• Ubiquitylation
• Sumoylation
• Acetylation
• ADP-ribosylation
• Ectodomain shedding
• miRNA
• Nucleocytoplasmic shuttling
• Signaling crosstalk

TGF-beta 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-beta 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-beta signaling occurs at multiple levels, including TGF-beta activation, formation, activation and destruction of functional TGF-beta 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-beta signal responses. These layers of regulation demonstrate how a simple signaling system can be coopted to exert exquisitely regulated, complex responses.