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TRAF6 negatively regulates the Jak1-Erk pathway in interleukin-2 signaling.
- Source :
-
Genes to Cells . Feb2011, Vol. 16 Issue 2, p179-189. 11p. - Publication Year :
- 2011
-
Abstract
- Tumor necrosis factor receptor-associated factor 6 (TRAF6) plays a critical role in establishing both innate and acquired immune responses by mediating signals from the TNF superfamily, the TLR/IL-1R family, and the T-cell receptor. Here, we report a previously unidentified function of TRAF6 in IL-2 signaling. CD3/CD28 stimulation-induced proliferation and Il2 mRNA expression in Traf6CD4 T cells were dramatically enhanced. This enhancement is likely due to hyperactive IL-2 signaling, in which activation of the Jak1-Erk pathway was enhanced and the subsequent Fos gene expression was up-regulated. To elucidate the molecular mechanisms of the enhanced activation of Jak1, IL-2 signaling was reconstituted in mouse embryonic fibroblast (MEF) cells to investigate the interaction between TRAF6 and the TRAF6-binding site that overlaps with the Jak1-binding site present in the IL-2R β-chain. The Jak1-Erk pathway was activated upon IL-2 stimulation in Traf6MEF cells, while a β-chain mutation that inactivates TRAF6 binding but retains Jak1 binding abrogated the TRAF6-dependent reduction in IL-2 signaling. These results indicate that the binding of TRAF6 to the TRAF6-binding site of the β-chain negatively regulates IL-2-induced Jak1 activation, which is likely to be involved in the proper regulation of T-cell activation and development. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13569597
- Volume :
- 16
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Genes to Cells
- Publication Type :
- Academic Journal
- Accession number :
- 57434872
- Full Text :
- https://doi.org/10.1111/j.1365-2443.2010.01474.x