Murine Schnurri-2 is required for positive selection of thymocytes.
A key step in T cell development involves the positive selection of cells that recognize antigen presented by self-major histocompatibility complex. Yet, the signals that are activated by T cell receptor engagement and lead to cell survival remain unclear. We show here that mice lacking the transcription factor Schnurri-2 (Shn-2), a large metal-finger protein, had severely defective positive selection of CD4+ and CD8+ cells. Drosophila Shn acts as a cofactor of Smad homolog and is required for Decapentaplegic signaling. Vertebrates have at least three Shn orthologs (Shn-1, Shn-2 and Shn-3), which are thought to act as nuclear targets in the bone morphogenetic protein-transforming growth factor-beta-activin signaling pathways. These data raised the possibility that the Smad-Shn-2 complex is involved in the thymic selection of T cells.
Takagi
T
T
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, CREST Research Project of JST, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Harada
J
J
Ishii
S
S
D028341:Activins / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D017637:Clonal Deletion / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D011828:Radiation Chimera; D017634:Self Tolerance / Q000502:physiology*; D015398:Signal Transduction; D051901:Smad4 Protein; D013045:Species Specificity; D013154:Spleen / Q000276:immunology / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C063232:HIVEP1 protein, human; C425103:HIVEP3 protein, human; C084779:Hivep3 protein, mouse; C112506:MAD protein, Drosophila; C112504:Med protein, Drosophila; D016328:NF-kappa B; D051901:Smad4 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C064196:dpp protein, Drosophila; C094066:shn protein, Drosophila; D028341:Activins; C077171:HIVEP2 protein, human