T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3.
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.
Hwang
Eun Sook
ES
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Szabo
Susanne J
SJ
Schwartzberg
Pamela L
PL
Glimcher
Laurie H
LH
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor; D015848:Interleukin-5 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020825:T-Box Domain Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000502:physiology*; D018417:Th1 Cells / Q000166:cytology / Q000502:physiology; D018418:Th2 Cells / Q000166:cytology / Q000502:physiology*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000098815:T-bet Transcription Factor
D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015848:Interleukin-5; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase