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Temporally regulated assembly of a dynamic signaling complex associated with the activated TCR
S Pacini1, S Valensin, J L Telford
1Department of Evolutionary Biology, University of Siena, Italy.
Abstract:
TCR triggering promotes multiple tyrosine kinase-dependent interactions involving proteins with one or more protein binding modules. Reported interactions mostly exceed the binding potential of these proteins. A solution to this paradox is the temporally regulated recruitment of alternative ligands. We have tested this hypothesis by analyzing the time course of protein/protein interactions triggered by TCR engagement. We show that a short-lived and dynamic multimolecular complex is assembled on tyrosine-phosphorylated CD3zeta. Specific components of this complex are recruited and shed in a temporal sequence distinct for each of the proteins analyzed. The temporally regulated assembly of a higher order structure at the activated TCR is likely to be crucial in achieving both signal longevity and signal specificity.
Insights
T-cell receptor (TCR) activation involves dynamic protein interactions. Temporally regulated assembly of signaling complexes ensures signal longevity and specificity.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- T-cell receptor (TCR) triggering initiates complex signaling cascades.
- Protein interactions mediated by tyrosine kinases are crucial for TCR signaling.
- Observed protein interactions often exceed the binding capacity of individual proteins, suggesting dynamic mechanisms.
Purpose of the Study:
- To investigate the hypothesis that temporally regulated recruitment of alternative ligands resolves the paradox of excessive protein interactions.
- To analyze the time course of protein-protein interactions following TCR engagement.
Main Methods:
- Time-course analysis of protein-protein interactions.
- Studying molecular complex assembly on tyrosine-phosphorylated CD3zeta following TCR engagement.
Main Results:
- A transient and dynamic multimolecular complex is assembled on tyrosine-phosphorylated CD3zeta upon TCR triggering.
- Individual protein components are recruited and released in a specific temporal sequence.
- This temporal recruitment pattern differs for each analyzed protein.
Conclusions:
- The temporally regulated assembly of higher-order structures at the activated TCR is essential for signal longevity.
- Dynamic complex assembly contributes to achieving signal specificity in T-cell activation.