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Math Biosci. 2012 Dec;240(2):187-200. doi: 10.1016/j.mbs.2012.07.005. Epub 2012 Aug 6.

Modularized Smad-regulated TGFβ signaling pathway.

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USRA, Division of Space Life Sciences, Houston, TX 77058, USA.


The transforming Growth Factor β (TGFβ) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. TGFβ 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 TGFβ receptors for degradation. In this work, we proposed a mathematical model to study the Smad-regulated TGFβ 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 TGFβ signaling pathway is discussed and supported as well by numerical simulation, indicating the robustness of the model.

[Indexed for MEDLINE]

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