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Related Experiment Video

Updated: Jul 18, 2026

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

Systems theory of Smad signalling.

D C Clarke¹, M D Betterton, X Liu

¹Department of Chemistry and Biochemistry , University of Colorado-Boulder, Boulder, CO 80309, USA.

Systems Biology

|December 26, 2006

Summary

Transforming growth factor-beta (TGFbeta) signaling relies on Smad proteins. Mathematical modeling reveals that unbalanced phosphorylation and dephosphorylation rates of Smad proteins are key to their nuclear accumulation during TGFbeta signaling.

Area of Science:

Cellular biology
Molecular signaling
Mathematical modeling

Background:

Transforming growth factor-beta (TGFbeta) signaling regulates cellular processes via Smad proteins.
Smad proteins translocate to the nucleus to control gene transcription upon TGFbeta stimulation.

Purpose of the Study:

To investigate the mechanisms governing Smad nuclear accumulation.
To develop a mathematical model of canonical Smad signaling.

Main Methods:

Constructed a mathematical model using published data and experimental Smad concentrations (Smad2, Smad3, Smad4).
Analyzed model sensitivity to various parameters and performed statistical analysis.
Simulated Smad nuclear accumulation with and without Smad4.

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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

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Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System

Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System

Published on: July 30, 2018

Related Experiment Videos

Last Updated: Jul 18, 2026

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

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Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System

Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System

Published on: July 30, 2018

Main Results:

Smad2 and Smad4 were present in higher cellular concentrations than Smad3 in mink lung epithelial cells.
Smad nuclear accumulation is highly sensitive to R-Smad phosphorylation/dephosphorylation rates and nuclear complex dynamics.
Rate-limiting phospho-R-Smad dephosphorylation emerged as a critical factor for Smad nuclear accumulation.

Conclusions:

An imbalance in R-Smad phosphorylation and dephosphorylation rates is a likely driver of Smad nuclear accumulation in TGFbeta signaling.
Constitutive nuclear binding factors are inefficient in mediating Smad nuclear accumulation if dephosphorylation is rapid.