ArticleCurrent biology : CB2003
Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP.
Article in Current biology : CB, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 131 citations in OpenAlex.
- A first-in-class Wiskott-Aldrich syndrome protein activator with antitumor activity in hematologic cancers.Haematologica · 2024Article
- ZAP-70 augments tonic B-cell receptor and CCR7 signaling in IGHV-unmutated chronic lymphocytic leukemia.Blood advances · 2024Article
- PI3K in T Cell Adhesion and Trafficking.Frontiers in immunology · 2021Review
- Multiple actin networks coordinate mechanotransduction at the immunological synapse.The Journal of cell biology · 2020Article
- Cdc42 Couples T Cell Receptor Endocytosis to GRAF1-Mediated Tubular Invaginations of the Plasma Membrane.Cells · 2019Article
- A negative role for the interleukin-2-inducible T-cell kinase (ITK) in human Foxp3+ TREG differentiation.PloS one · 2019Article
- Crk adaptor proteins mediate actin-dependent T cell migration and mechanosensing induced by the integrin LFA-1.Science signaling · 2018Article
- Polarity of CD4+ T cells towards the antigen presenting cell is regulated by the Lck adapter TSAd.Scientific reports · 2018Article
- IL-2 Inducible Kinase ITK is Critical for HIV-1 Infection of Jurkat T-cells.Scientific reports · 2018Article
- eNOS S-nitrosylates β-actin on Cys374 and regulates PKC-θ at the immune synapse by impairing actin binding to profilin-1.PLoS biology · 2017Article
- Inducible T Cell Kinase Regulates the Acquisition of Cytolytic Capacity and Degranulation in CD8Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Computational spatiotemporal analysis identifies WAVE2 and cofilin as joint regulators of costimulation-mediated T cell actin dynamics.Science signaling · 2016Article
- Non-cleavable talin rescues defect in the T-cell conjugation of T-cells deficient in the immune adaptor SKAP1.Immunology letters · 2016Article
- Itk signals promote neuroinflammation by regulating CD4+ T-cell activation and trafficking.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Discs Large Homolog 1 Splice Variants Regulate p38-Dependent and -Independent Effector Functions in CD8+ T Cells.PloS one · 2015Article
- Signal Integration during T Lymphocyte Activation and Function: Lessons from the Wiskott-Aldrich Syndrome.Frontiers in immunology · 2015Review
- Innate PLZF+CD4+ αβ T cells develop and expand in the absence of Itk.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Coordinate control of cytoskeletal remodeling and calcium mobilization during T-cell activation.Immunological reviews · 2013Review
- Actin-mediated feedback loops in B-cell receptor signaling.Immunological reviews · 2013Review
- The actin cytoskeleton coordinates the signal transduction and antigen processing functions of the B cell antigen receptor.Frontiers in biology · 2013Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Actin polymerization at the immune synapse is required for T cell activation and effector function; however, the relevant regulatory pathways remain poorly understood. We showed previously that binding to antigen presenting cells (APCs) induces localized activation of Cdc42 and Wiskott-Aldrich Syndrome protein (WASP) at the immune synapse. Several lines of evidence suggest that Tec kinases could interact with WASP-dependent actin regulatory processes. Since T cells from Rlk-/-, Itk-/-, and Rlk-/- x Itk-/- mice have defects in signaling and development, we asked whether Itk or Rlk function in actin polymerization at the immune synapse. We find that Itk-/- and Rlk-/- x Itk-/- T cells are defective in actin polymerization and conjugate formation in response to antigen-pulsed APCs. Itk functions downstream of the TCR, since similar defects were observed upon TCR engagement alone. Using conformation-specific probes, we show that although the recruitment of WASP and Arp2/3 complex to the immune synapse proceeds normally, the localized activation of Cdc42 and WASP is defective. Finally, we find that the defect in Cdc42 activation likely stems from a requirement for Itk in the recruitment of Vav to the immune synapse. Our results identify Itk as a key element of the pathway leading to localized actin polymerization at the immune synapse.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.