title: Comment on "Controlling long-term signaling: receptor dynamics determine attenuation and refractory behavior of the TGF-β pathway"-Smad2/3 activity does not predict the dynamics of transcription.
abstract: 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.
authors.affiliation: Center for Studies in Physics and Biology, The Rockefeller University, New York, NY 10065, USA. Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, NY 10065, USA. aryeh.warmflash@rice.edu.
authors.forename: Aryeh
authors.initials: A
authors.lastname: Warmflash
authors.affiliation: Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Qixiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Brivanlou
authors.affiliation: Center for Studies in Physics and Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Siggia
mesh_terms: D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases