Abstract
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.
MeSH terms
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Activins / physiology
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Animals
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Bone Marrow Cells / metabolism
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Bone Marrow Transplantation
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Bone Morphogenetic Proteins / physiology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Clonal Deletion / physiology*
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Drosophila Proteins / physiology
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Drosophila melanogaster / embryology
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Drosophila melanogaster / genetics
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Epithelial Cells / cytology
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Female
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Gene Expression Regulation, Developmental
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Gene Targeting
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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NF-kappa B / metabolism
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Radiation Chimera
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Self Tolerance / physiology*
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Signal Transduction
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Smad4 Protein
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Species Specificity
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Spleen / immunology
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Spleen / pathology
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Stromal Cells / metabolism
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / pathology*
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Thymus Gland / immunology
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Thymus Gland / pathology*
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Thymus Gland / transplantation
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Trans-Activators / genetics
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Trans-Activators / physiology
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Transcription Factors / physiology
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Transforming Growth Factor beta / physiology
Substances
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Bone Morphogenetic Proteins
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Carrier Proteins
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DNA-Binding Proteins
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Drosophila Proteins
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HIVEP1 protein, human
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HIVEP3 protein, human
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Hivep3 protein, mouse
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MAD protein, Drosophila
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Med protein, Drosophila
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NF-kappa B
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Smad4 Protein
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Trans-Activators
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Transcription Factors
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Transforming Growth Factor beta
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dpp protein, Drosophila
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shn protein, Drosophila
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Activins
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HIVEP2 protein, human