Mathematical Modeling and Analysis of Crosstalk between MAPK Pathway and Smad-Dependent TGF-β Signal Transduction

Broad evidence exists for cross talk between the Mitogen-activated protein kinases (MAPK) pathway and Smad-dependent TGF-β signal transduction. A variety of studies, oftentimes involving different cell types, have identified several potential mechanisms for the crosstalk. However, there is no clear consensus on the actual mechanism(s) responsible for the crosstalk. This work develops a model of the pathway, including several hypothesized crosstalk mechanisms, and discusses which of the potential mechanisms can appropriately describe observed behaviors. Simulation results show a good agreement of the findings with results reported in the literature.