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.

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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