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| Status |
Public on Feb 02, 2011 |
| Title |
The kinases MEKK2 and MEKK3 regulate Transforming Growth Factor-β-mediated helper T cell differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Mitogen-activated protein kinases (MAPKs) are key mediators of the T cell receptor (TCR) signals but their roles in T helper (Th) cell differentiation are unclear. Here we showed that the MAPK kinase kinases MEKK2 (encoded by Map3k2) and MEKK3 (encoded by Map3k3),negatively regulated transforming growth factor-beta (TGF-beta)-mediated Th cell differentiation.Map3k2-/-Map3k3Lck-Cre/- mice showed an abnormal accumulation of regulatory T (Treg) and Th17 cells in the periphery, consistent with Map3k2-/-Map3k3Lck-Cre/- naïve CD4+ T cells' differentiation into Treg and Th17 cells with a higher frequency than wild-type (WT) cells after TGF-beta stimulation in vitro. In addition, Map3k2-/-Map3k3Lck-Cre/- mice developed more severe experimental autoimmune encephalomyelitis. Map3k2-/-Map3k3Lck-Cre/- T cells exhibited impaired phosphorylation of the SMAD2 and SMAD3 proteins at their linker regions, which negatively regulated the TGF-beta responses in T cells. Thus, the crosstalk between TCR-induced MAPK and the TGF-beta signaling pathways is important in regulating Th cell differentiation.
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| Overall design |
CD4+CD62L-CD44+ cells were FACS sorted from C57BL/6 Lck-Cre MEKK2 KO MEKK3F/-(dKO) or C57BL/6 WT mice
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| Contributor(s) |
Chang X, Su B |
| Citation(s) |
21333552 |
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| Submission date |
Jan 31, 2011 |
| Last update date |
Jan 16, 2019 |
| Contact name |
xing chang |
| Organization name |
Yale University
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| Street address |
10 Amistad street, RM414
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| City |
new haven |
| ZIP/Postal code |
CT |
| Country |
USA |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA135937 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE26987_RAW.tar |
15.8 Mb |
(http)(custom) |
TAR |
| GSE26987_non-normalized.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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