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

E Sebzda, M Bracke, T Tugal, N Hogg… - Nature immunology, 2002 - nature.com
E Sebzda, M Bracke, T Tugal, N Hogg, DA Cantrell
Nature immunology, 2002nature.com
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 …
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 β1 and β2 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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