Regulation of TGF-ß Signal Transduction

Zhao, Bing; Chen, Ye-Guang

For Smad regulation, many questions await to be addressed too. It is well documented that the TGF- receptor-mediated C-terminal phosphorylation of Smad2/3 is the key event for Smad activation. TGF-receptors can also induce the Smad2/3 phosphorylation in the linker region [104, 105] . The linker phosphorylation has been shown to inhibit Smad activity or induce Smad degradation [6] . How the inhibitory linker phosphorylation and the activating Cterminal phosphorylation are coordinated is unknown. In the nucleus, Smad7 can bind to DNA via its MH2 domain and inhibit TGF--driven transcription by interfering with the R-Smad/Smad4-DNA association. It will be interesting to investigate whether Smad7 has other function independent of inhibition of TGF-signaling. Regulation of TGF-signaling has been extensively investigated. However, as TGF-signaling controls a wide range of biological responses and distinct regulatory mechanism is employed by different tissue at different time, exploration of the molecular mechanisms of how the TGFsignaling is modulated in specific pathological or physiological processes will be an exciting field.