ABIN-2 is required for optimal activation of Erk MAP kinase in innate immune responses.journal article
Papoutsopoulou S, Symons A, Tharmalingham T, Belich MP, Kaiser F, Kioussis D, O'Garra A, Tybulewicz V, Ley SC.
Nat Immunol. 2006 Jun;7(6):606-15. Epub 2006 Apr 23.
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-kappaB 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-kappaB. 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 1beta. Thus, ABIN-2 acts to positively regulate the Erk signaling potential by stabilizing TPL-2.