Identification of pro-interleukin 16 as a novel target of MAP kinases in activated T lymphocytes

Arian Laurence, Emmanuelle Astoul, Sarah Hanrahan, Nick Totty, Doreen Cantrell (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    T lymphocyte activation is controlled by a coordinated web of tyrosine and serine kinases. There is a large body of information about tyrosine kinase substrates in T cells but analysis of serine kinase substrates has been more difficult. Recently we described an antiserum that recognizes serine-phosphorylated peptides corresponding to the substrate sequences for AGC serine kinases. This antiserum, termed PAP-1 (phospho antibody for proteomics-1), has proven useful for probing the serine phosphoproteome of antigen receptor-activated T lymphocytes. The present study shows that PAP-1 can also be used to explore serine kinases activated by cytokines and chemokines in T cells. Using PAP-1, together with proteomic analysis, the precursor form of the cytokine IL-16 (ProIL-16) was shown to be phosphorylated on Ser144 in antigen receptor-, SDF1α- and IL-2-activated T cells. Genetic and pharmacological-inhibitor experiments showed that the phosphorylation of ProIL-16 is dependent on activation of the kinases Erk1/2. IL-16 is secreted by mitogen-activated T cells, and the biochemical link between ProIL-16 and Erk1/2, revealed by studies with PAP-1, prompted analysis of the role of MAP kinases in this response. We show that TCR-mediated secretion of IL-16 is dependent on MAP kinases. The present study thus reveals how phosphoproteomic analysis opens previously unrecognized avenues for research, and yields novel insights about targets for MAP kinases in T lymphocytes.

    Original languageEnglish
    Pages (from-to)587-597
    Number of pages11
    JournalEuropean Journal of Immunology
    Volume34
    Issue number2
    DOIs
    Publication statusPublished - 1 Feb 2004

    Keywords

    • IL-16
    • IL-2
    • SDF1α
    • Serine kinases
    • T cell receptor

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