Smad signaling dynamics: insights from a parsimonious model.
The molecular mechanisms that transmit information from cell surface receptors to the nucleus are exceedingly complex; thus, much effort has been expended in developing computational models to understand these processes. A recent study on modeling the nuclear-cytoplasmic shuttling of Smad2-Smad4 complexes in response to transforming growth factor-beta (TGF-beta) receptor activation has provided substantial insight into how this signaling network translates the degree of TGF-beta receptor activation (input) into the amount of nuclear Smad2-Smad4 complexes (output). The study addressed this question by combining a simple, mechanistic model with targeted experiments, an approach that proved particularly powerful for exploring the fundamental properties of a complex signaling network. The mathematical model revealed that Smad nuclear-cytoplasmic dynamics enables a proportional but time-delayed coupling between the input and the output. As a result, the output can faithfully track gradual changes in the input while the rapid input fluctuations that constitute signaling noise are dampened out.
Shankaran
Harish
H
Systems Biology Program, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Wiley
H Steven
HS
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D051901:Smad4 Protein / Q000378:metabolism*
D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; D051901:Smad4 Protein