Regulation of TGF-ß Signal Transduction

Zhao, Bing; Chen, Ye-Guang

Transforming growth factor-(TGF-) family is a group of structurally related growth factors, which includes TGF-, activin, nodal, bone morphogenetic proteins (BMPs), and others. These growth factors play critical roles in regulating a wide range of biological processes during embryonic development and adult tissue homeostasis, and deregulation of the signal transduction has been associated with many human diseases, including cancer and tissue fibrosis [1] [2] [3] . TGF-signaling is initiated by the binding of TGF-to its serine and threonine kinase receptors, the type II and type I receptors on the cell membrane. Ligand binding triggers the formation of the receptor heterocomplex, in which type II receptor phosphorylates type I receptor at the threonine and serine residues in its TTSGSGSG motif, leading to the activation of type I receptor [1, 4, 5] . The activated type I receptor recruits and phosphorylates the R-Smad proteins, which then form a heterocomplex with the co-Smad Smad4. The Smad complexes are then accumulated in the nucleus and regulate transcription of the target genes by cooperating with other cofactors [6, 7] .