scholarly journals A Role for Wiskott-Aldrich Syndrome Protein in T-cell Receptor-mediated Transcriptional Activation Independent of Actin Polymerization

2001 ◽  
Vol 276 (24) ◽  
pp. 21450-21457 ◽  
Author(s):  
Christopher Silvin ◽  
Barbara Belisle ◽  
Arie Abo
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Transcriptional Activation ◽  
Actin Polymerization ◽  
Cell Receptor ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

T-cell receptor ligation causes Wiskott-Aldrich syndrome protein degradation and F-actin assembly downregulation

2013 ◽  
Vol 132 (3) ◽  
pp. 648-655.e1 ◽  
Author(s):  
Yuko Watanabe ◽  
Yoji Sasahara ◽  
Narayanaswamy Ramesh ◽  
Michel J. Massaad ◽  
Chung Yeng Looi ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Degradation ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Actin Assembly ◽  
Wiskott Aldrich Syndrome ◽  
Receptor Ligation ◽  
Syndrome Protein

scholarly journals Fyn and PTP-PEST–mediated Regulation of Wiskott-Aldrich Syndrome Protein (WASp) Tyrosine Phosphorylation Is Required for Coupling T Cell Antigen Receptor Engagement to WASp Effector Function and T Cell Activation

2004 ◽  
Vol 199 (1) ◽  
pp. 99-112 ◽  
Author(s):  
Karen Badour ◽  
Jinyi Zhang ◽  
Fabio Shi ◽  
Yan Leng ◽  
Michael Collins ◽  
...  
Keyword(s):  
T Cell ◽  
Tyrosine Phosphorylation ◽  
T Cell Activation ◽  
Actin Polymerization ◽  
Cell Activation ◽  
Synapse Formation ◽  
Tyrosine Phosphatase ◽  
Structural Constraints ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

Involvement of the Wiskott-Aldrich syndrome protein (WASp) in promoting cell activation requires its release from autoinhibitory structural constraints and has been attributed to WASp association with activated cdc42. Here, however, we show that T cell development and T cell receptor (TCR)-induced proliferation and actin polymerization proceed normally in WASp−/− mice expressing a WASp transgene lacking the cdc42 binding domain. By contrast, mutation of tyrosine residue Y291, identified here as the major site of TCR-induced WASp tyrosine phosphorylation, abrogated induction of WASp tyrosine phosphorylation and its effector activities, including nuclear factor of activated T cell transcriptional activity, actin polymerization, and immunological synapse formation. TCR-induced WASp tyrosine phosphorylation was also disrupted in T cells lacking Fyn, a kinase shown here to bind, colocalize with, and phosphorylate WASp. By contrast, WASp was tyrosine dephosphorylated by protein tyrosine phosphatase (PTP)-PEST, a tyrosine phosphatase shown here to interact with WASp via proline, serine, threonine phosphatase interacting protein (PSTPIP)1 binding. Although Fyn enhanced WASp-mediated Arp2/3 activation and was required for synapse formation, PTP-PEST combined with PSTPIP1 inhibited WASp-driven actin polymerization and synapse formation. These observations identify key roles for Fyn and PTP-PEST in regulating WASp and imply that inducible WASp tyrosine phosphorylation can occur independently of cdc42 binding, but unlike the cdc42 interaction, is absolutely required for WASp contributions to T cell activation.

scholarly journals T Cell Receptor-induced Nuclear Factor κB (NF-κB) Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-mediated Calcium Entry

2016 ◽  
Vol 291 (16) ◽  
pp. 8440-8452 ◽  
Author(s):  
Xiaohong Liu ◽  
Corbett T. Berry ◽  
Gordon Ruthel ◽  
Jonathan J. Madara ◽  
Katelyn MacGillivray ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Transcriptional Activation ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Calcium Entry ◽  
Nuclear Factor

scholarly journals Actin and agonist MHC–peptide complex–dependent T cell receptor microclusters as scaffolds for signaling

2005 ◽  
Vol 202 (8) ◽  
pp. 1031-1036 ◽  
Author(s):  
Gabriele Campi ◽  
Rajat Varma ◽  
Michael L. Dustin
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Actin Polymerization ◽  
Kinase Inhibitor ◽  
Cell Receptor ◽  
Intercellular Adhesion Molecule ◽  
Cell Contact ◽  
Intercellular Adhesion Molecule 1 ◽  
Planar Bilayers ◽  
Latrunculin A

T cell receptor (TCR) microclusters form within seconds of T cell contact with supported planar bilayers containing intercellular adhesion molecule-1 and agonist major histocompatibility complex (MHC)–peptide complexes, and elevation of cytoplasmic Ca2+ is observed within seconds of the first detectable microclusters. At 0–30 s after contact, TCR microclusters are colocalized with activated forms of Lck, ZAP-70, and the linker for activation of T cells. By 2 min, activated kinases are reduced in the older central microclusters, but are abundant in younger peripheral microclusters. By 5 min, TCR in the central supramolecular activation cluster have reduced activated kinases, whereas faint peripheral TCR microclusters efficiently generated activated Lck and ZAP-70. TCR microcluster formation is resistant to inhibition by Src family kinase inhibitor PP2, but is abrogated by actin polymerization inhibitor latrunculin A. We propose that Src kinase–independent formation of TCR microclusters in response to agonist MHC–peptide provides an actin-dependent scaffold for signal amplification.

scholarly journals 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

2000 ◽  
Vol 149 (1) ◽  
pp. 181-194 ◽  
Author(s):  
Matthias Krause ◽  
Antonio S. Sechi ◽  
Marlies Konradt ◽  
David Monner ◽  
Frank B. Gertler ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Actin Cytoskeleton ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
T Cell Signaling ◽  
Tcr Signaling ◽  
Activated T Cells ◽  
Antigen Presenting ◽  
Syndrome Protein

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.

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