Protein kinase D2 is a digital amplifier of T cell receptor-stimulated diacylglycerol signaling in naïve CD8+ T cells

María N. Navarro, Carmen Feijoo-Carnero, Alba Gonzalez Arandilla, Matthias Trost, Doreen A. Cantrell (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    Abstract

    Protein kinase D2 (PKD2) is a serine and threonine kinase that is activated in T cells by diacylglycerol and protein kinase C in response to stimulation of the T cell receptor (TCR) by antigen. We quantified the activation of PKD2 at the single-cell level and found that this kinase acts as a sensitive digital amplifier of TCR engagement, enabling CD8(+) T cells to match the production of inflammatory cytokines to the quality and quantity of TCR ligands. There was a digital response pattern of PKD2 activation in response to TCR engagement, such that increasing the concentration and potency of TCR ligands increased the number of cells that exhibited activated PKD2. However, for each cell that responded to TCR stimulation, the entire cellular pool of PKD2 (~400,000 molecules) was activated. Moreover, PKD2 acted as an amplification checkpoint for antigen-stimulated digital cytokine responses and translated the differential strength of TCR signaling to determine the number of naïve CD8(+) T cells that became effector cells. Together, these results provide insights into PKD family kinases and how they act digitally to amplify signaling networks controlled by the TCR.
    Original languageEnglish
    Article numberra99
    Number of pages12
    JournalScience Signaling
    Volume7
    Issue number348
    DOIs
    Publication statusPublished - 21 Oct 2014

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    T-cells
    Diglycerides
    T-Cell Antigen Receptor
    T-Lymphocytes
    Phosphotransferases
    Chemical activation
    Diacylglycerol Kinase
    Cytokines
    Ligands
    protein kinase D2
    Protein-Serine-Threonine Kinases
    Protein Kinase C
    Amplification
    Cell Count
    Antigens
    Molecules

    Cite this

    Navarro, María N. ; Feijoo-Carnero, Carmen ; Gonzalez Arandilla, Alba ; Trost, Matthias ; Cantrell, Doreen A. / Protein kinase D2 is a digital amplifier of T cell receptor-stimulated diacylglycerol signaling in naïve CD8+ T cells. In: Science Signaling. 2014 ; Vol. 7, No. 348.
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    abstract = "Protein kinase D2 (PKD2) is a serine and threonine kinase that is activated in T cells by diacylglycerol and protein kinase C in response to stimulation of the T cell receptor (TCR) by antigen. We quantified the activation of PKD2 at the single-cell level and found that this kinase acts as a sensitive digital amplifier of TCR engagement, enabling CD8(+) T cells to match the production of inflammatory cytokines to the quality and quantity of TCR ligands. There was a digital response pattern of PKD2 activation in response to TCR engagement, such that increasing the concentration and potency of TCR ligands increased the number of cells that exhibited activated PKD2. However, for each cell that responded to TCR stimulation, the entire cellular pool of PKD2 (~400,000 molecules) was activated. Moreover, PKD2 acted as an amplification checkpoint for antigen-stimulated digital cytokine responses and translated the differential strength of TCR signaling to determine the number of na{\"i}ve CD8(+) T cells that became effector cells. Together, these results provide insights into PKD family kinases and how they act digitally to amplify signaling networks controlled by the TCR.",
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    Protein kinase D2 is a digital amplifier of T cell receptor-stimulated diacylglycerol signaling in naïve CD8+ T cells. / Navarro, María N.; Feijoo-Carnero, Carmen; Gonzalez Arandilla, Alba ; Trost, Matthias; Cantrell, Doreen A. (Lead / Corresponding author).

    In: Science Signaling, Vol. 7, No. 348, ra99, 21.10.2014.

    Research output: Contribution to journalArticle

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    AU - Navarro, María N.

    AU - Feijoo-Carnero, Carmen

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    AU - Trost, Matthias

    AU - Cantrell, Doreen A.

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    AB - Protein kinase D2 (PKD2) is a serine and threonine kinase that is activated in T cells by diacylglycerol and protein kinase C in response to stimulation of the T cell receptor (TCR) by antigen. We quantified the activation of PKD2 at the single-cell level and found that this kinase acts as a sensitive digital amplifier of TCR engagement, enabling CD8(+) T cells to match the production of inflammatory cytokines to the quality and quantity of TCR ligands. There was a digital response pattern of PKD2 activation in response to TCR engagement, such that increasing the concentration and potency of TCR ligands increased the number of cells that exhibited activated PKD2. However, for each cell that responded to TCR stimulation, the entire cellular pool of PKD2 (~400,000 molecules) was activated. Moreover, PKD2 acted as an amplification checkpoint for antigen-stimulated digital cytokine responses and translated the differential strength of TCR signaling to determine the number of naïve CD8(+) T cells that became effector cells. Together, these results provide insights into PKD family kinases and how they act digitally to amplify signaling networks controlled by the TCR.

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