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14‐3‐3 Proteins Bind Both Filamin and α L β 2 Integrin in Activated T Cells
Author(s) -
NURMI SUSANNA M.,
GAHMBERG CARL G.,
FAGERHOLM SUSANNA C.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.035
Subject(s) - microbiology and biotechnology , integrin , filamin , actin cytoskeleton , integrin alpha m , cytoskeleton , cell adhesion , cd18 , integrin, beta 6 , t cell receptor , signal transducing adaptor protein , signal transduction , biology , cd49c , chemistry , t cell , receptor , cell , biochemistry , immunology , immune system
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 (αLβ2 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 β 2 integrins and filamin. The integrin β 2 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.