First Author | Sebzda E | Year | 2002 |
Journal | Nat Immunol | Volume | 3 |
Issue | 3 | Pages | 251-8 |
PubMed ID | 11836528 | Mgi Jnum | J:74992 |
Mgi Id | MGI:2159527 | Doi | 10.1038/ni765 |
Citation | Sebzda E, et al. (2002) Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling. Nat Immunol 3(3):251-8 |
abstractText | 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. |