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Science 307 (5708): 430-433

Copyright © 2005 by the American Association for the Advancement of Science

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

Eun Sook Hwang,1 Susanne J. Szabo,1* Pamela L. Schwartzberg,3 Laurie H. Glimcher1,2{dagger}

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.

1 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
2 Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
3 National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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* Present address: Novartis Pharmaceuticals, Cambridge, MA 02115, USA.

{dagger} To whom correspondence should be addressed. E-mail: lglimche{at}hsph.harvard.edu


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