The transforming growth factor-β (TGF-β) pathway plays a fundamental role in development and disease. Despite its importance, the dynamics of signaling activity downstream of ligand stimulation have remained largely unexplored. The recent study by Vizán et al. demonstrates that loss of signaling-capable receptors from the cell surface leads to a refractory period during which cells are incapable of responding to additional signals. In this letter and in our previous work, we show that although receptor dynamics determine Smad2/3 activity, signaling activity at the level of transcription terminates far earlier in a receptor- and Smad2/3-independent manner. Thus, Smad2/3 activity does not reveal the dynamics of transcription, and downstream measures must be examined directly.
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