Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells

Maria N. Navarro, Linda V. Sinclair, Carmen Feijoo-Carnero, Rosemary Clarke, Sharon A. Matthews, Doreen A. Cantrell

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    PKD (protein kinase D) 2 is a serine/threonine kinase activated by diacylglycerol in response to engagement of antigen receptors in lymphocytes. To explore PKD2 regulation and function in TCR (T-cell antigen receptor) signal transduction we expressed TCR complexes with fixed affinity for self antigens in the T-cells of PKD2-null mice or mice deficient in PKD2 catalytic activity.We also developed a single cell assay to quantify PKD2 activation as T-cells respond to developmental stimuli or engagement of a/ß TCR complexes in vivo. Strikingly, PKD2 loss caused increases in thymic output, lymphadenopathy and splenomegaly in TCR transgenic mice. The precise magnitude and timing of PKD2 activation during T-cell development is thus critical to regulate thymic homoeostasis. PKD2-null T-cells that exit the thymus have a normal transcriptome, but show a limited and abnormal transcriptional response to antigen. Transcriptional profiling reveals the full consequences of PKD2 loss and maps in detail the selective, but critical, function for PKD2 in signalling by a/ß mature TCR complexes in peripheral T-cells.
    Original languageEnglish
    Pages (from-to)649-659
    Number of pages11
    JournalBiochemical Journal
    Volume442
    Issue number3
    Early online date10 Jan 2012
    DOIs
    Publication statusPublished - 15 Mar 2012

    Fingerprint

    T-cells
    T-Cell Antigen Receptor
    T-Lymphocytes
    Chemical activation
    Thymus
    Null Lymphocytes
    Signal transduction
    Antigen Receptors
    Lymphocytes
    Protein-Serine-Threonine Kinases
    Diglycerides
    Splenomegaly
    Autoantigens
    Transcriptome
    Thymus Gland
    Transgenic Mice
    Assays
    Signal Transduction
    Catalyst activity
    Homeostasis

    Keywords

    • Cytokine
    • Lymphocyte
    • Pre-cell antigen receptor
    • Protein kinase D (PKD)
    • T-cell antigen receptor (TCR)
    • Thymus

    Cite this

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    title = "Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells",
    abstract = "PKD (protein kinase D) 2 is a serine/threonine kinase activated by diacylglycerol in response to engagement of antigen receptors in lymphocytes. To explore PKD2 regulation and function in TCR (T-cell antigen receptor) signal transduction we expressed TCR complexes with fixed affinity for self antigens in the T-cells of PKD2-null mice or mice deficient in PKD2 catalytic activity.We also developed a single cell assay to quantify PKD2 activation as T-cells respond to developmental stimuli or engagement of a/{\ss} TCR complexes in vivo. Strikingly, PKD2 loss caused increases in thymic output, lymphadenopathy and splenomegaly in TCR transgenic mice. The precise magnitude and timing of PKD2 activation during T-cell development is thus critical to regulate thymic homoeostasis. PKD2-null T-cells that exit the thymus have a normal transcriptome, but show a limited and abnormal transcriptional response to antigen. Transcriptional profiling reveals the full consequences of PKD2 loss and maps in detail the selective, but critical, function for PKD2 in signalling by a/{\ss} mature TCR complexes in peripheral T-cells.",
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    Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells. / Navarro, Maria N.; Sinclair, Linda V.; Feijoo-Carnero, Carmen; Clarke, Rosemary; Matthews, Sharon A.; Cantrell, Doreen A.

    In: Biochemical Journal, Vol. 442, No. 3, 15.03.2012, p. 649-659.

    Research output: Contribution to journalArticle

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    AU - Navarro, Maria N.

    AU - Sinclair, Linda V.

    AU - Feijoo-Carnero, Carmen

    AU - Clarke, Rosemary

    AU - Matthews, Sharon A.

    AU - Cantrell, Doreen A.

    N1 - Copyright 2012 Elsevier B.V., All rights reserved.

    PY - 2012/3/15

    Y1 - 2012/3/15

    N2 - PKD (protein kinase D) 2 is a serine/threonine kinase activated by diacylglycerol in response to engagement of antigen receptors in lymphocytes. To explore PKD2 regulation and function in TCR (T-cell antigen receptor) signal transduction we expressed TCR complexes with fixed affinity for self antigens in the T-cells of PKD2-null mice or mice deficient in PKD2 catalytic activity.We also developed a single cell assay to quantify PKD2 activation as T-cells respond to developmental stimuli or engagement of a/ß TCR complexes in vivo. Strikingly, PKD2 loss caused increases in thymic output, lymphadenopathy and splenomegaly in TCR transgenic mice. The precise magnitude and timing of PKD2 activation during T-cell development is thus critical to regulate thymic homoeostasis. PKD2-null T-cells that exit the thymus have a normal transcriptome, but show a limited and abnormal transcriptional response to antigen. Transcriptional profiling reveals the full consequences of PKD2 loss and maps in detail the selective, but critical, function for PKD2 in signalling by a/ß mature TCR complexes in peripheral T-cells.

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