Modularized Smad-regulated TGFβ signaling pathway

The transforming Growth Factor beta (TGF beta) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. TGF beta signaling can be induced by several factors including ionizing radiation. The pathway is regulated in a negative feedback loop through promoting the nuclear import of the regulatory Smads and a subsequent expression of inhibitory Smad7, that forms ubiquitin ligase with Smurf2, targeting active TGF beta receptors for degradation. In this work, we proposed a mathematical model to study the Smad-regulated TGF beta signaling pathway. By modularization, we are able to analyze mathematically each component subsystem and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, in the TGF beta signaling pathway is discussed and supported as well by numerical simulation, indicating the robustness of the model. Published by Elsevier Inc.