ABIN-2 is required for optimal activation of Erk MAP kinase in innate immune responses
ABIN-2 is required for optimal activation of Erk MAP kinase in innate immune responses
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DOI：
10.1038/ni1334
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发表时间：
2006-06-01
影响因子：
30.5
通讯作者：
Ley, Steven C.
中科院分区：
文献类型：
--
作者：
Papoutsopoulou, Stamatia;Symons, Antony;Ley, Steven C.
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-kappa B 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-kappa B. 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 1 beta. Thus, ABIN-2 acts to positively regulate the Erk signaling potential by stabilizing TPL-2.
