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Xu M , Sharma A , Wiest DL , Sen JM
Pre-TCR-Induced beta-Catenin Facilitates Traversal through beta-Selection
Journal of Immunology. 2009 Jan;182(2) :751-758
PMID: ISI:000262390600003 PMCID: PMC 2657338
AbstractPre-TCR induced signals regulate development of the alpha beta 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. The Journal of Immunology, 2009, 182: 751-758.
NotesXu, Mai Sharma, Archna Wiest, David L. Sen, Jyoti Misra 59 AMER ASSOC IMMUNOLOGISTS; 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA 393RO