Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actin-Related Protein 2
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Actin-Related Protein 3
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Actins / antagonists & inhibitors
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Actins / metabolism*
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Blood Platelets / cytology
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism*
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Cell Adhesion Molecules / chemistry
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Cell Adhesion Molecules / metabolism*
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Cloning, Molecular
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Cytoskeletal Proteins*
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Cytoskeleton / metabolism*
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Humans
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Lymphocyte Activation
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Microfilament Proteins
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Molecular Sequence Data
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Oncogene Proteins / metabolism
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Phosphoproteins / chemistry
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Phosphoproteins / metabolism*
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Protein Binding
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Protein Isoforms / chemistry
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Protein Isoforms / metabolism
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Proteins / metabolism
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Pseudopodia / metabolism
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Receptor Aggregation
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Receptors, Antigen, T-Cell / metabolism*
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Signal Transduction*
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / ultrastructure
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Tumor Cells, Cultured
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Wiskott-Aldrich Syndrome Protein
Substances
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ACTR2 protein, human
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ACTR3 protein, human
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Actin-Related Protein 2
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Actin-Related Protein 3
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Actins
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Cell Adhesion Molecules
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Cytoskeletal Proteins
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FYB1 protein, human
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Microfilament Proteins
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Nck protein
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Oncogene Proteins
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Phosphoproteins
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Protein Isoforms
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Proteins
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Receptors, Antigen, T-Cell
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SLP-76 signal Transducing adaptor proteins
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WAS protein, human
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Wiskott-Aldrich Syndrome Protein
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vasodilator-stimulated phosphoprotein