| First Author | Kovalovsky D | Year | 2009 |
| Journal | J Immunol | Volume | 183 |
| Issue | 6 | Pages | 3873-84 |
| PubMed ID | 19717519 | Mgi Jnum | J:152395 |
| Mgi Id | MGI:4358642 | Doi | 10.4049/jimmunol.0901369 |
| Citation | Kovalovsky D, et al. (2009) Beta-catenin/Tcf determines the outcome of thymic selection in response to alphabetaTCR signaling. J Immunol 183(6):3873-84 |
| abstractText | Thymic maturation of T cells depends on the intracellular interpretation of alphabetaTCR signals by processes that are poorly understood. In this study, we report that beta-catenin/Tcf signaling was activated in double-positive thymocytes in response to alphabetaTCR engagement and impacted thymocyte selection. TCR engagement combined with activation of beta-catenin signaled thymocyte deletion, whereas Tcf-1 deficiency rescued from negative selection. Survival/apoptotis mediators including Bim, Bcl-2, and Bcl-x(L) were alternatively influenced by stabilization of beta-catenin or ablation of Tcf-1, and Bim-mediated beta-catenin induced thymocyte deletion. TCR activation in double-positive cells with stabilized beta-catenin triggered signaling associated with negative selection, including sustained overactivation of Lat and Jnk and a transient activation of Erk. These observations are consistent with beta-catenin/Tcf signaling acting as a switch that determines the outcome of thymic selection downstream the alphabetaTCR cascade. |
