Pre-TCR-induced beta-catenin facilitates traversal through beta-selection.
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.
Xu
Mai
M
Lymphocyte Development Unit, Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Sharma
Archna
A
Wiest
David L
DL
Sen
Jyoti Misra
JM
D021581:Active Transport, Cell Nucleus / Q000276:immunology; D000818:Animals; D018801:CD2 Antigens / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D051776:Early Growth Response Protein 3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011498:Protein Precursors / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051176:beta Catenin / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
D018801:CD2 Antigens; C497369:Egr3 protein, mouse; D011498:Protein Precursors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051176:beta Catenin; D051776:Early Growth Response Protein 3