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T Helper Cell Fate Specified by Kinase-Mediated Interaction of T-bet with GATA-3

Science  21 Jan 2005:
Vol. 307, Issue 5708, pp. 430-433
DOI: 10.1126/science.1103336

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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.

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