| Autor: |
Zou, Qiang, Jin, Jin, Xiao, Yichuan, Hu, Hongbo, Zhou, Xiaofei, Jie, Zuliang, Xie, Xiaoping, Li, James Y.H., Cheng, Xuhong, Sun, Shao-Cong |
| Zdroj: |
The Journal of Experimental Medicine; July 2015, Vol. 212 Issue: 8 p1323-1336, 14p |
| Abstrakt: |
Generation of T lymphocytes in the thymus is guided by signal transduction from the T cell receptor (TCR), but the underlying mechanism is incompletely understood. Here we have identified a Golgi-associated factor, TRAF3-interacting protein 3 (TRAF3IP3), as a crucial mediator of thymocyte development. TRAF3IP3 deficiency in mice attenuates the generation of mature thymocytes caused by impaired thymocyte-positive selection. TRAF3IP3 mediates TCR-stimulated activation of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) and its upstream kinase mitogen/extracellular signal-regulated kinase (MEK). Interestingly, TRAF3IP3 exerts this signaling function through recruiting MEK to the Golgi and, thereby, facilitating the interaction of MEK with its activator BRAF. Transgenic expression of a constitutively active MEK rescues the T cell development block in Traf3ip3 knockout mice. These findings establish TRAF3IP3 as a novel regulator of T cell development and suggest a Golgi-specific ERK signaling mechanism that regulates thymocyte development. |
| Databáze: |
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