期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 283, 期 42, 页码 28216-28225出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M804174200
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology [20060003, 17390139, 20590485, 19659121, 19890041]
- Ministry of Health, Labor and Welfar, the Kanae Foundation, the Uehara Memorial Foundation, the Astellas Foundation, and the Sagawa Foundation
- Grants-in-Aid for Scientific Research [19890041, 17390139, 19659121, 20060003, 20590485] Funding Source: KAKEN
The differentiation of naive CD4 T cells into Th2 cells requires the T cell receptor-mediated activation of the ERK MAPK cascade. Little is known, however, in regard to how the ERK MAPK cascade regulates Th2 cell differentiation. We herein identified Gfi1 (growth factor independent-1) as a downstream target of the ERK MAPK cascade for Th2 cell differentiation. In the absence of Gfi1, interleukin-5 production and the change of histone modification at the interleukin-5 gene locus were severely impaired. Furthermore, the interferon gamma gene showed a striking activation in the Gfi1(-/-) Th2 cells. An enhanced ubiquitin/proteasome-dependent degradation of GATA3 protein was observed in Gfi1(-/-) Th2 cells, and the overexpression of GATA3 eliminated the defect of Th2 cell function in Gfi1-deficient Th2 cells. These data suggest that the T cell receptor-mediated induction of Gfi1 controls Th2 cell differentiation through the regulation of GATA3 protein stability.
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