The self-limiting dynamics of TGF-β signaling in silico and in vitro, with negative feedback through PPM1A upregulation.

ABSTRACT: The TGF-β/Smad signaling system decreases its activity through strong negative regulation. Several molecular mechanisms of negative regulation have been published, but the relative impact of each mechanism on the overall system is unknown. In this work, we used computational and experimental methods to assess multiple negative regulatory effects on Smad signaling in HaCaT cells. Previously reported negative regulatory effects were classified by time-scale: degradation of phosphorylated R-Smad and I-Smad-induced receptor degradation were slow-mode effects, and dephosphorylation of R-Smad was a fast-mode effect. We modeled combinations of these effects, but found no combination capable of explaining the observed dynamics of TGF-β/Smad signaling. We then proposed a negative feedback loop with

SUBMITTER: Wang J 

PROVIDER: S-EPMC4105941 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature