First Author | Xu M | Year | 2009 |
Journal | J Immunol | Volume | 182 |
Issue | 2 | Pages | 751-8 |
PubMed ID | 19124717 | Mgi Jnum | J:143501 |
Mgi Id | MGI:3827044 | Doi | 10.4049/jimmunol.182.2.751 |
Citation | Xu M, et al. (2009) Pre-TCR-induced beta-catenin facilitates traversal through beta-selection. J Immunol 182(2):751-8 |
abstractText | Pre-TCR induced signals regulate development of the alphabeta TCR lineage cells at the beta-selection checkpoint. We have previously shown that conditional deletion of beta-catenin, a central mediator of Wnt-beta-catenin-T cell factor signaling pathway, impairs traversal through the beta-selection checkpoint. We now provide a molecular basis for the impairment. We demonstrate that pre-TCR signals specifically stabilize beta-catenin in CD4-CD8- double negative thymocytes during beta-selection. Pre-TCR induced Erk activity was required to stabilize beta-catenin. Enforced expression of stabilized beta-catenin was sufficient to mediate aspects of beta-selection including sustained expression of early growth response (Egr) genes. Consistently, deletion of beta-catenin reduced induction of Egr gene expression by the pre-TCR signal and blocked efficient beta-selection. Thus, we demonstrate that pre-TCR induced beta-catenin sustains expression of Egr genes that facilitate traversal through the beta-selection checkpoint. |