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PMID:20696860

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Citation

Cook, KD and Miller, J (2010) TCR-dependent translational control of GATA-3 enhances Th2 differentiation. J. Immunol. 185:3209-16

Abstract

The differentiation of CD4(+) T cells into the Th2 subset is controlled by the transcription factor GATA-3. GATA-3 is both necessary and sufficient for Th2 differentiation and works through the induction of chromatin remodeling at the Th2 effector cytokine loci. We show in this study that IL-4 stimulation induces GATA-3 mRNA upregulation, but the level of GATA-3 protein induced is insufficient for Th2 differentiation. The levels of GATA-3 protein and Th2 differentiation are enhanced by concomitant TCR signaling through the PI3K/mammalian target of rapamycin pathway. The PI3K-mediated increase in GATA-3 protein occurs without increasing the GATA-3 mRNA level. Rather, TCR signaling through PI3K specifically enhances the translation rate of GATA-3 without affecting the protein stability. Importantly, this role of TCR signaling is independent of the effects of TCR signaling in T cell survival and expansion. Thus, TCR signaling through PI3K may play a critical role in Th2 differentiation by the specific enhancement of GATA-3 translation.

Links

PubMed Online version:10.4049/jimmunol.0902544

Keywords

Animals; Antigen Presentation/genetics; Antigen Presentation/immunology; Cell Differentiation/genetics; Cell Differentiation/immunology; Cells, Cultured; GATA3 Transcription Factor/genetics; GATA3 Transcription Factor/metabolism; GATA3 Transcription Factor/physiology; Humans; Lymphocyte Activation/genetics; Lymphocyte Activation/immunology; Mice; Mice, Inbred BALB C; Mice, Transgenic; Peptide Chain Elongation, Translational/genetics; Peptide Chain Elongation, Translational/immunology; RNA, Messenger/biosynthesis; Receptors, Antigen, T-Cell/genetics; Receptors, Antigen, T-Cell/physiology; Signal Transduction/genetics; Signal Transduction/immunology; Th2 Cells/cytology; Th2 Cells/immunology; Th2 Cells/metabolism; Up-Regulation/genetics; Up-Regulation/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GATA3

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GATA3

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GATA3

involved_in

GO:0031929: TOR signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GATA3

involved_in

GO:0014065: phosphatidylinositol 3-kinase signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GATA3

involved_in

GO:0045582: positive regulation of T cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GATA3

involved_in

GO:0050852: T cell receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GATA3

involved_in

GO:0071353: cellular response to interleukin-4

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IL4

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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