Pre-TCR-induced beta-catenin facilitates traversal through beta-selection
Xu, M.; Sharma, A.; Wiest, D.L.; Sen, J.Misra.
Journal of Immunology 182(2): 751-758
2009
ISSN/ISBN: 0022-1767 PMID: 19124717 Document Number: 631045
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.