Abstract
The early growth response gene 1 (Egr-1) is induced during positive selection in the thymus and has been implicated in the differentiation of CD4+ thymocytes. Here, we show that signals that specifically direct CD8 lineage commitment also induce Egr-1 DNA-binding activity in the nucleus. However, we find that pharmacological inhibition of mitogen-activated protein kinase/extracellular signal-related kinase kinase activity potently inhibits Egr-1 DNA-binding function at concentrations that promote differentiation of CD8+ thymocytes, suggesting Egr-1 activity is not essential for CD8 commitment. To further determine the role of Egr-1 in thymocyte development, we compare steady-state Egr-1 DNA-binding activity in thymocytes from mice with defined defects in positive selection. The data indicate that the appearance of functional Egr-1 is downstream of signals induced by TCR/MHC engagement, whereas it is less sensitive to alterations in Lck-mediated signals, and does not correlate directly with proficient positive selection. Egr-1 is one of the earliest transcription factors induced upon TCR ligation on immature thymocytes, and plays a potential role in the transcription of genes involved in thymocyte selection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / enzymology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism*
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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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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Early Growth Response Protein 1
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Gene Expression Regulation / immunology*
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Immediate-Early Proteins*
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Ligands
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MAP Kinase Signaling System / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Organ Culture Techniques
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Protein Binding / genetics
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Protein Binding / immunology
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism*
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Thymus Gland / cytology*
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Thymus Gland / enzymology
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Thymus Gland / immunology
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Thymus Gland / metabolism*
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Transcription Factors / biosynthesis*
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcriptional Activation
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ras Proteins / physiology
Substances
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DNA-Binding Proteins
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Early Growth Response Protein 1
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Egr1 protein, mouse
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Immediate-Early Proteins
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Ligands
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Receptors, Antigen, T-Cell
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Transcription Factors
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ras Proteins