MSK regulate TCR-induced CREB phosphorylation but not immediate early gene transcription

Madlen Kaiser, Giselle R. Wiggin, Kurt Lightfoot, J. Simon C. Arthur, Andrew Macdonald

    Research output: Contribution to journalArticle

    20 Citations (Scopus)

    Abstract

    Stimulation of the T cell receptor activates the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) cascades. We demonstrate that TCR stimulation also activates the mitogen- and stress-activated kinases (MSK) downstream of ERK1/2 and p38 in both a T cell line and primary peripheral T cells. MSK1/2-knockout mice were found to have normal numbers of T cells in the thymus, and development of these cells appeared unaffected. Using naive T cells and T lymphoblasts from MSK1/2-knockout mice, it was found that MSK was the kinase responsible for phosphorylation of the transcription factor CREB in response to TCR stimulation. Phosphorylation of CREB by MSK has been linked to the transcription of nur77, nor1 and c-fos downstream of MAPK signalling in various cell types. In T cells, the TCR-dependent transcription of these genes was found to require a MAPK-dependent but MSK-independent signalling pathway. Nevertheless, the number of T cells present in the spleens of MSK1/2-knockout mice and the IL-2-induced proliferation of these cells was reduced compared to wild-type mice. This correlated to a reduction in the TCR-induced up-regulation of the IL-2 receptor CD25 and a requirement for MSK in IL-2-induced CREB phosphorylation.

    Original languageEnglish
    Pages (from-to)2583-95
    Number of pages13
    JournalEuropean Journal of Immunology
    Volume37
    Issue number9
    DOIs
    Publication statusPublished - Sep 2007

    Keywords

    • Animals
    • Cell Differentiation
    • Cell Line
    • Cell Proliferation
    • Cyclic AMP Response Element-Binding Protein
    • Enzyme Activation
    • Gene Expression Regulation
    • Mice
    • Phosphorylation
    • Receptors, Antigen, T-Cell
    • Ribosomal Protein S6 Kinases, 90-kDa
    • T-Lymphocytes
    • Thymus Gland
    • Time Factors
    • Transcription, Genetic

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