Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling

Eric Sebzda, Madelon Bracke, Tamara Tugal, Nancy Hogg, Doreen Ann Cantrell

    Research output: Contribution to journalArticle

    235 Citations (Scopus)

    Abstract

    T cell receptor (TCR) stimulation activates the small GTPase Rap1A, which is reported to antagonize Ras signaling and induces T cell anergy. To address its role in vivo, we generated transgenic mice that constitutively expressed active Rap1A within the T cell lineage. We found that active Rap1A did not interfere with the Ras signaling pathway or antagonize T cell activation. Instead of anergy, the T lymphocytes that constitutively expressed active Rap1A showed enhanced TCR-mediated responses, both in thymocytes and mature T cells. In addition, Rap1A activation was sufficient to induce strong activation of the 1 and 2 integrins via an avidity-modulation mechanism. This shows that, far from playing an inhibitory role during T cell activation, Rap1A positively influences T cells by augmenting lymphocyte responses and directing integrin activation.
    Original languageEnglish
    Pages (from-to)251-258
    Number of pages8
    JournalNature Immunology
    Volume3
    Issue number3
    DOIs
    Publication statusPublished - 2002

    Keywords

    • T lymphocytes

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