| Autor: |
Papoutsopoulou, Stamatia, Symons, Antony, Tharmalingham, Tharsana, Belich, Monica P, Kaiser, Frank, Kioussis, Dimitris, O'Garra, Anne, Tybulewicz, Victor, Ley, Steven C. |
| Předmět: |
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| Zdroj: |
Nature Immunology; Jun2006, Vol. 7 Issue 6, p606-615, 10p, 5 Graphs |
| Abstrakt: |
The TPL-2 MEK kinase is essential for activation of the Erk MAP kinase pathway during innate immune responses. TPL-2 is found in complex with ABIN-2 (A20-binding inhibitor of NF-κB 2). Here, using antigen-presenting cells from ABIN-2-deficient mice, we show that ABIN-2 was required for optimal activation of Erk induced by receptors that signal via TPL-2, including Toll-like receptor 4 and tumor necrosis factor receptor 1 in macrophages, and CD40 in B cells. ABIN-2 was necessary for the maintenance of TPL-2 protein stability. In contrast, ABIN-2 deficiency did not affect agonist-induced regulation of transcription factor NF-κB. Stimulation of ABIN-2-deficient macrophages via Toll-like receptor 4 showed that different thresholds of Erk signaling were required for optimal induction of tumor necrosis factor and interleukin 1β. Thus, ABIN-2 acts to positively regulate the Erk signaling potential by stabilizing TPL-2. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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