Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA. yshi@molbio.princeton.edu
TGF-beta signaling controls a plethora of cellular responses and figures prominently in animal development. Recent cellular, biochemical, and structural studies have revealed significant insight into the mechanisms of the activation of TGF-beta receptors through ligand binding, the activation of Smad proteins through phosphorylation, the transcriptional regulation of target gene expression, and the control of Smad protein activity and degradation. This article reviews these latest advances and presents our current understanding on the mechanisms of TGF-beta signaling from cell membrane to the nucleus.