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  • Title: Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling.
    Author: Sebzda E, Bracke M, Tugal T, Hogg N, Cantrell DA.
    Journal: Nat Immunol; 2002 Mar; 3(3):251-8. PubMed ID: 11836528.
    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 beta1 and beta2 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.
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