14-3-3 proteins bind both filamin and alphaLbeta2 integrin in activated T cells.
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.
Nurmi
Susanna M
SM
Division of Biochemistry, Faculty of Biosciences, PB 56 (Viikinkaari 5D), 00014 University of Helsinki, Helsinki, Finland.
Gahmberg
Carl G
CG
Fagerholm
Susanna C
SC
D048948:14-3-3 Proteins / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003285:Contractile Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D064448:Filamins; D006801:Humans; D047468:Immunoprecipitation; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011485:Protein Binding; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D048948:14-3-3 Proteins; D003285:Contractile Proteins; D064448:Filamins; D016169:Lymphocyte Function-Associated Antigen-1; D008840:Microfilament Proteins; D015240:Phorbol 12,13-Dibutyrate