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.
Krause
M
M
Department of Cell Biology, Gesellschaft für Biotechnologische Forschung (GBF), D-38124 Braunschweig, Germany.
Sechi
A S
AS
Konradt
M
M
Monner
D
D
Gertler
F B
FB
Wehland
J
J
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000166:cytology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D011940:Receptor Aggregation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D051316:Wiskott-Aldrich Syndrome Protein; D000098662:Vasodilator-Stimulated Phosphoprotein
C495926:ACTR2 protein, human; C495928:ACTR3 protein, human; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C106957:FYB1 protein, human; D008840:Microfilament Proteins; C078332:Nck protein; D015513:Oncogene Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D000098662:Vasodilator-Stimulated Phosphoprotein