Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the Arp2/3 complex link T cell receptor (TCR) signaling to the actin cytoskeleton.
T cell receptor (TCR)-driven activation of helper T cells induces a rapid polarization of their cytoskeleton towards bound antigen presenting cells (APCs). We have identified the Fyn- and SLP-76-associated protein Fyb/SLAP as a new ligand for Ena/ vasodilator-stimulated phosphoprotein (VASP) homology 1 (EVH1) domains. Upon TCR engagement, Fyb/SLAP localizes at ... the interface between T cells and anti-CD3-coated beads, where Evl, a member of the Ena/VASP family, Wiskott-Aldrich syndrome protein (WASP) and the Arp2/3 complex are also found. In addition, Fyb/SLAP is restricted to lamellipodia of spreading platelets. In activated T cells, Fyb/SLAP associates with Ena/VASP family proteins and is present within biochemical complexes containing WASP, Nck, and SLP-76. Inhibition of binding between Fyb/SLAP and Ena/VASP proteins or WASP and the Arp2/3 complex impairs TCR-dependent actin rearrangement, suggesting that these interactions play a key role in linking T cell signaling to remodeling of the actin cytoskeleton.
Mesh Terms:
Actin-Related Protein 2, Actin-Related Protein 3, Actins, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Blood Platelets, Carrier Proteins, Cell Adhesion Molecules, Cloning, Molecular, Cytoskeletal Proteins, Cytoskeleton, Humans, Lymphocyte Activation, Microfilament Proteins, Molecular Sequence Data, Oncogene Proteins, Phosphoproteins, Protein Binding, Protein Isoforms, Proteins, Pseudopodia, Receptor Aggregation, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Tumor Cells, Cultured, Wiskott-Aldrich Syndrome Protein
Actin-Related Protein 2, Actin-Related Protein 3, Actins, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Blood Platelets, Carrier Proteins, Cell Adhesion Molecules, Cloning, Molecular, Cytoskeletal Proteins, Cytoskeleton, Humans, Lymphocyte Activation, Microfilament Proteins, Molecular Sequence Data, Oncogene Proteins, Phosphoproteins, Protein Binding, Protein Isoforms, Proteins, Pseudopodia, Receptor Aggregation, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Tumor Cells, Cultured, Wiskott-Aldrich Syndrome Protein
J. Cell Biol.
Date: Apr. 03, 2000
PubMed ID: 10747096
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