The serine kinase phosphoinositide-dependent kinase 1 (PDK1) regulates T cell development

    Research output: Contribution to journalArticle

    92 Citations (Scopus)

    Abstract

    T lymphocyte activation is associated with activation of diverse AGC serine kinases (named after family members protein kinase A, protein kinase G and protein kinase C). It has been difficult to assess the function of these molecules in T cell development with simple gene-deletion strategies because different isoforms of AGC kinases are coexpressed in the thymus and have overlapping, redundant functions. To circumvent these problems, we explored the consequences of genetic manipulation of phosphoinositide-dependent kinase 1 (PDK1), a rate-limiting 'upstream' activator of AGC kinases. Here we analyzed the effect of PDK1 deletion on T lineage development. We also assessed the consequences of reducing PDK1 levels to 10% of normal. Complete PDK1 loss blocked T cell differentiation in the thymus, whereas reduced PDK1 expression allowed T cell differentiation but blocked proliferative expansion. These studies show that AGC family kinases are essential for T cell development.
    Original languageEnglish
    Pages (from-to)539-545
    Number of pages7
    JournalNature Immunology
    Volume5
    Issue number5
    DOIs
    Publication statusPublished - 2004

    Fingerprint

    1-Phosphatidylinositol 4-Kinase
    Protein-Serine-Threonine Kinases
    T-Lymphocytes
    Cyclic GMP-Dependent Protein Kinases
    Phosphotransferases
    Thymus Gland
    Cell Differentiation
    Gene Deletion
    Lymphocyte Activation
    Cyclic AMP-Dependent Protein Kinases
    GTP-Binding Proteins
    Protein Kinase C
    Protein Isoforms

    Keywords

    • T lymphocytes
    • Cell development

    Cite this

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    title = "The serine kinase phosphoinositide-dependent kinase 1 (PDK1) regulates T cell development",
    abstract = "T lymphocyte activation is associated with activation of diverse AGC serine kinases (named after family members protein kinase A, protein kinase G and protein kinase C). It has been difficult to assess the function of these molecules in T cell development with simple gene-deletion strategies because different isoforms of AGC kinases are coexpressed in the thymus and have overlapping, redundant functions. To circumvent these problems, we explored the consequences of genetic manipulation of phosphoinositide-dependent kinase 1 (PDK1), a rate-limiting 'upstream' activator of AGC kinases. Here we analyzed the effect of PDK1 deletion on T lineage development. We also assessed the consequences of reducing PDK1 levels to 10{\%} of normal. Complete PDK1 loss blocked T cell differentiation in the thymus, whereas reduced PDK1 expression allowed T cell differentiation but blocked proliferative expansion. These studies show that AGC family kinases are essential for T cell development.",
    keywords = "T lymphocytes, Cell development",
    author = "Hinton, {Heather J.} and Alessi, {Dario R.} and Cantrell, {Doreen A.}",
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    The serine kinase phosphoinositide-dependent kinase 1 (PDK1) regulates T cell development. / Hinton, Heather J.; Alessi, Dario R.; Cantrell, Doreen A.

    In: Nature Immunology, Vol. 5, No. 5, 2004, p. 539-545.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The serine kinase phosphoinositide-dependent kinase 1 (PDK1) regulates T cell development

    AU - Hinton, Heather J.

    AU - Alessi, Dario R.

    AU - Cantrell, Doreen A.

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    AB - T lymphocyte activation is associated with activation of diverse AGC serine kinases (named after family members protein kinase A, protein kinase G and protein kinase C). It has been difficult to assess the function of these molecules in T cell development with simple gene-deletion strategies because different isoforms of AGC kinases are coexpressed in the thymus and have overlapping, redundant functions. To circumvent these problems, we explored the consequences of genetic manipulation of phosphoinositide-dependent kinase 1 (PDK1), a rate-limiting 'upstream' activator of AGC kinases. Here we analyzed the effect of PDK1 deletion on T lineage development. We also assessed the consequences of reducing PDK1 levels to 10% of normal. Complete PDK1 loss blocked T cell differentiation in the thymus, whereas reduced PDK1 expression allowed T cell differentiation but blocked proliferative expansion. These studies show that AGC family kinases are essential for T cell development.

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