Abstract
Gads, a hematopoietic-lineage-specific Grb2 family member, is involved in the signaling mediated by the TCR through its interactions with SLP-76 and LAT. Here, we generated transgenic mice expressing Grf40-dSH2, an SH2-deleted dominant-negative form of Gads, which is driven by the lck proximal promoter. The total number of thymocytes was profoundly reduced in the transgenic mice, whereas in the double-negative (CD4(-)CD8(-)) thymocyte subset, in particular the CD25(+)CD44(-) pre-T cell population, it was significantly increased. However, CD5 expression, which is mediated by pre-TCR stimulation, was significantly suppressed on the CD4(-)CD8(-) thymocytes of the transgenic mice. Furthermore, the SLP-76-dependent signaling was markedly suppressed as well. These data suggest that Gads plays an important role in the pre-TCR as well as TCR signaling in thymocytes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Carrier Proteins / physiology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Lineage / genetics
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Cell Lineage / immunology
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Cells, Cultured
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Female
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Gene Expression Regulation, Developmental* / genetics
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Genes, Dominant* / immunology
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Growth Inhibitors / genetics*
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Growth Inhibitors / physiology
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Humans
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Lymphocyte Activation / genetics
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Phosphoproteins / genetics
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Phosphoproteins / physiology
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Sequence Deletion / genetics
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Signal Transduction / genetics
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Signal Transduction / immunology
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Stem Cells / cytology
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Stem Cells / immunology
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology
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Thymus Gland / cytology
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Thymus Gland / embryology
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Thymus Gland / growth & development*
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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GRAP2 protein, human
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Growth Inhibitors
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Mona protein, mouse
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Phosphoproteins
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SLP-76 signal Transducing adaptor proteins