Pre-TCR induced signals regulate development of the αβ TCR lineage cells at the β-selection checkpoint. We have previously shown that conditional deletion of β-catenin, a central mediator of Wnt-β-catenin-T cell factor signaling pathway, impairs traversal through the β-selection checkpoint. We now provide a molecular basis for the impairment. We demonstrate that pre-TCR signals specifically stabilize β-catenin in CD4-CD8- double negative thymocytes during β-selection. Pre-TCR induced Erk activity was required to stabilize β-catenin. Enforced expression of stabilized β-catenin was sufficient to mediate aspects of β-selection including sustained expression of early growth response (Egr) genes. Consistently, deletion of β-catenin reduced induction of Egr gene expression by the pre-TCR signal and blocked efficient β-selection. Thus, we demonstrate that pre-TCR induced β-catenin sustains expression of Egr genes that facilitate traversal through the β-selection checkpoint.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Immunology|
|State||Published - Jan 15 2009|
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