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
Activins/physiology
Animals
Bone Marrow Cells/metabolism
Bone Marrow Transplantation
Bone Morphogenetic Proteins/physiology
CD4-Positive T-Lymphocytes/cytology,immunology
CD8-Positive T-Lymphocytes/cytology,immunology
Carrier Proteins/genetics,physiology
Clonal Deletion/physiology
DNA-Binding Proteins/deficiency,genetics,physiology
Drosophila Proteins/physiology
Drosophila melanogaster/embryology,genetics
Epithelial Cells/cytology
Female
Gene Expression Regulation, Developmental
Gene Targeting
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B/metabolism
Radiation Chimera
Self Tolerance/physiology
Signal Transduction
Smad4 Protein
Species Specificity
Spleen/immunology,pathology
Stromal Cells/metabolism
T-Lymphocyte Subsets/immunology,pathology
Thymus Gland/immunology,pathology,transplantation
Trans-Activators/genetics,physiology
Transcription Factors/physiology
Transforming Growth Factor beta/physiology
Chemicals
Bone Morphogenetic Proteins
Carrier Proteins
DNA-Binding Proteins
Drosophila Proteins
HIVEP1 protein, human
HIVEP3 protein, human
Hivep3 protein, mouse
MAD protein, Drosophila
Med protein, Drosophila
NF-kappa B
Smad4 Protein
Trans-Activators
Transcription Factors
Transforming Growth Factor beta
dpp protein, Drosophila
shn protein, Drosophila
Activins
HIVEP2 protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Takagi T
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, CREST Research Project of JST, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Harada J
Ishii S