ABIN-2 is required for optimal activation of Erk MAP kinase in innate immune responses

Stamatia Papoutsopoulou, Antony Symons, Tharsana Tharmalingham, Monica P. Belich, Frank Kaiser, Dimitris Kioussis, Anne O'Garra, Victor Tybulewicz, Steven C. Ley*

*Corresponding author for this work
65 Citations (Scopus)


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.

Original languageEnglish
JournalNature Immunology
Issue number6
Pages (from-to)606-615
Number of pages10
Publication statusPublished - 06.2006

Research Areas and Centers

  • Research Area: Medical Genetics


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