Abstract
Cell lineage specification depends on both gene activation and gene silencing, and in the differentiation of T helper progenitors to Th1 or Th2 effector cells, this requires the action of two opposing transcription factors, T-bet and GATA-3. T-bet is essential for the development of Th1 cells, and GATA-3 performs an equivalent role in Th2 development. We report that T-bet represses Th2 lineage commitment through tyrosine kinase-mediated interaction between the two transcription factors that interferes with the binding of GATA-3 to its target DNA. These results provide a novel function for tyrosine phosphorylation of a transcription factor in specifying alternate fates of a common progenitor cell.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Differentiation
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Cell Lineage
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Cytokines / pharmacology
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Cytokines / physiology
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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GATA3 Transcription Factor
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Interleukin-5 / genetics
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Mice
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Mice, Inbred BALB C
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Mutation
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Phosphorylation
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Phosphotyrosine / metabolism
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Promoter Regions, Genetic
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Protein Structure, Tertiary
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Protein-Tyrosine Kinases / metabolism
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T-Box Domain Proteins
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / physiology*
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Th1 Cells / cytology
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Th1 Cells / physiology
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Th2 Cells / cytology
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Th2 Cells / physiology*
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Cytokines
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DNA-Binding Proteins
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GATA3 Transcription Factor
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Gata3 protein, mouse
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Interleukin-5
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Trans-Activators
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Transcription Factors
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Phosphotyrosine
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Protein-Tyrosine Kinases
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emt protein-tyrosine kinase