Antigen receptor regulation of phosphoinositide-dependent kinase 1 pathways during thymocyte development

Heather J. Hinton, Rosemary G. Clarke, Doreen A. Cantrell (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    Phosphoinositide-dependent kinase 1 (PDK1) is essential for T cell development but little is know about the stimuli that regulate PDK1 signaling in vivo. The thymus contains a heterogeneous mixture of cells at different stages of development making it difficult to use biochemical techniques to examine the activity of PDK1 pathways as thymocytes develop in situ. Herein, we use a single cell assay to quantify activation of the PDK1 target kinase ribosomal S6 kinase 1 (S6K1) in different murine thymocyte subsets immediately ex vivo. This technique allows an assessment of S6K1 activation as thymocytes respond to developmental stimuli in vivo. These studies reveal that only a small percentage of thymocytes show evidence for activation of PDK1 mediated signaling in situ. The thymic subpopulations that contain active PDK1/S6K1 are those known to be responding to signaling by the pre T cell receptor and the mature alpha/beta T cell antigen receptor (TCR). Moreover, loss of antigen receptor signaling in T cell progenitors that cannot rearrange their TCR beta locus prevents in vivo activation of S6K1. The present data identifying antigen receptor signaling as a key activator of PDK1 mediated signaling afford a molecular explanation for the important role of this molecule in T cells.

    Original languageEnglish
    Pages (from-to)5845-5850
    Number of pages6
    JournalFEBS Letters
    Volume580
    Issue number25
    DOIs
    Publication statusPublished - 30 Oct 2006

    Keywords

    • Kinase
    • PDK1
    • Pre T cell receptor
    • S6K1
    • Signal transduction
    • T cell receptor
    • TCR signaling
    • Thymocyte
    • Thymus

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