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Updated: Jul 16, 2026

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
14-3-3 proteins bind both filamin and alphaLbeta2 integrin in activated T cells
Susanna M Nurmi1, Carl G Gahmberg, Susanna C Fagerholm
1Division of Biochemistry, Faculty of Biosciences, PB 56 (Viikinkaari 5D), 00014 University of Helsinki, Helsinki, Finland.
Abstract:
Engagement of the T cell receptor (TCR) initiates intracellular signaling cascades that result in T cell activation, differentiation, acquisition of effector functions, or apoptosis. The signals from the TCR are coupled to distal signaling pathways by adapter proteins leading to dramatic changes in the cytoskeleton, transcription, and activation of integrins, which mediate adhesion. LFA-1 (leukocyte function-associated antigen-1) integrin (alphaLbeta2 or CD11a/CD18) plays an important role in adhesion, for example, by linking extracellular ligands to the actin cytoskeleton. The intracellular tails of integrins contain several phosphorylation sites, making them candidate-binding partners for 14-3-3 proteins, which are adaptor proteins that bind to phosphorylated ligands. In a screen for 14-3-3 binding partners in T cells, we identified both beta2 integrins and filamin. The integrin beta2 chain binds to 14-3-3 proteins through phosphorylated Thr758 after TCR ligation and this association regulates integrin-mediated cell spreading, which is necessary for adhesion. Here, we show that filamin associates with 14-3-3 proteins in activated T cells. 14-3-3 association with T cell membrane and cytoskeleton proteins after cell stimulation may mediate numerous T cell functions.
Insights
T cell receptor (TCR) signaling involves adapter proteins like 14-3-3. This study shows 14-3-3 proteins bind to filamin in activated T cells, impacting cell adhesion and function.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- T cell receptor (TCR) engagement triggers signaling cascades crucial for T cell activation and function.
- Adapter proteins, including 14-3-3 proteins, couple TCR signals to downstream pathways affecting the cytoskeleton and cell adhesion.
- Integrins, such as LFA-1 (leukocyte function-associated antigen-1), mediate cell adhesion by linking extracellular ligands to the cytoskeleton.
Purpose of the Study:
- To investigate the interaction of 14-3-3 proteins with filamin in activated T cells.
- To understand the role of these interactions in T cell signaling and function.
Main Methods:
- Screening for 14-3-3 binding partners in T cells.
- Investigating the association of filamin with 14-3-3 proteins in activated T cells.
- Analyzing the role of integrin beta2 phosphorylation and 14-3-3 binding in T cell spreading and adhesion.
Main Results:
- Beta2 integrins and filamin were identified as 14-3-3 binding partners in T cells.
- The integrin beta2 chain binds to 14-3-3 proteins via phosphorylated Thr758 upon TCR ligation, regulating cell spreading and adhesion.
- Filamin was shown to associate with 14-3-3 proteins in activated T cells.
Conclusions:
- 14-3-3 proteins bind to phosphorylated beta2 integrins and filamin in activated T cells.
- These associations are critical for regulating integrin-mediated cell spreading and adhesion.
- 14-3-3 interactions with T cell membrane and cytoskeleton proteins likely mediate diverse T cell functions.
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