Related Experiment Video
Updated: Jan 23, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
TGF-β family ligands exhibit distinct signalling dynamics that are driven by receptor localisation
Daniel S J Miller1, Bernhard Schmierer2, Caroline S Hill3
1Developmental Signalling Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Abstract:
Growth factor-induced signal transduction pathways are tightly regulated at multiple points intracellularly, but how cells monitor levels of extracellular ligand and translate this information into appropriate downstream responses remains unclear. Understanding signalling dynamics is thus a key challenge in determining how cells respond to external cues. Here, we demonstrate that different TGF-β family ligands, namely activin A and BMP4, signal with distinct dynamics, which differ profoundly from those of TGF-β itself. The signalling dynamics are driven by differences in the localisation and internalisation of receptors for each ligand, which in turn determine the capability of cells to monitor levels of extracellular ligand. By using mathematical modelling, we demonstrate that the distinct receptor behaviours and signalling dynamics observed may be primarily driven by differences in ligand-receptor affinity. Furthermore, our results provide a clear rationale for the different mechanisms of pathway regulation found in vivo for each of these growth factors.
Insights
Cells monitor extracellular ligand levels through distinct signaling dynamics of TGF-β family ligands, driven by receptor behavior and ligand-receptor affinity. This explains in vivo pathway regulation differences.
Area of Science:
- Cellular signaling
- Molecular biology
- Biophysics
Background:
- Cellular responses to external cues depend on understanding extracellular ligand levels.
- Signal transduction pathways are regulated intracellularly, but extracellular monitoring mechanisms are unclear.
- Distinct transforming growth factor-beta (TGF-β) family ligands exhibit unique signaling dynamics.
Purpose of the Study:
- To investigate how cells monitor extracellular ligand levels and translate this into downstream responses.
- To compare the signaling dynamics of different TGF-β family ligands: activin A, BMP4, and TGF-β.
- To elucidate the mechanisms driving distinct signaling dynamics and their implications for pathway regulation.
Main Methods:
- Experimental observation of ligand-receptor interactions, localization, and internalization.
- Mathematical modeling to analyze signaling dynamics and receptor behavior.
- Comparative analysis of activin A, BMP4, and TGF-β signaling.
Main Results:
- Activin A and BMP4 exhibit distinct signaling dynamics, differing significantly from TGF-β.
- Differences in receptor localization and internalization drive these distinct signaling dynamics.
- Ligand-receptor affinity is a primary determinant of observed receptor behaviors and signaling dynamics.
Conclusions:
- Cellular monitoring of extracellular ligand levels is achieved through ligand-specific receptor dynamics.
- Distinct signaling dynamics of TGF-β family ligands are governed by receptor behavior and ligand-receptor affinity.
- These findings provide a rationale for the differential in vivo regulation mechanisms of these growth factors.
Related Concept Videos
01:16TGF - β Signaling Pathway
02:47Protein Families
01:57Gene Families
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
01:26Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
01:31Internal Receptors
00:49Ligand Binding and Linkage