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PMID:16633345

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Citation

Papoutsopoulou, S, Symons, A, Tharmalingham, T, Belich, MP, Kaiser, F, Kioussis, D, O'Garra, A, Tybulewicz, V and Ley, SC (2006) ABIN-2 is required for optimal activation of Erk MAP kinase in innate immune responses. Nat. Immunol. 7:606-15

Abstract

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.

Links

PubMed Online version:10.1038/ni1334

Keywords

Adaptor Proteins, Signal Transducing/deficiency; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/physiology; Animals; Antigens, CD40/metabolism; B-Lymphocytes/immunology; Early Growth Response Protein 1/metabolism; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases/metabolism; Immunity, Innate; Interleukin-1/metabolism; Lipopolysaccharides/immunology; MAP Kinase Kinase Kinases/metabolism; Macrophages/immunology; Mice; Mice, Mutant Strains; NF-kappa B/metabolism; Proto-Oncogene Proteins/metabolism; Receptors, Tumor Necrosis Factor, Type I/metabolism; Toll-Like Receptor 4/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TNIP2

involved_in

GO:0023035: CD40 signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TNIP2

involved_in

GO:0034162: toll-like receptor 9 signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TNIP2

involved_in

GO:0034138: toll-like receptor 3 signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TNIP2

involved_in

GO:0034134: toll-like receptor 2 signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TNIP2

involved_in

GO:0050871: positive regulation of B cell activation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TNIP2

involved_in

GO:0050821: protein stabilization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TNIP2

involved_in

GO:0043032: positive regulation of macrophage activation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TNIP2

involved_in

GO:0071222: cellular response to lipopolysaccharide

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TNIP2

involved_in

GO:0070498: interleukin-1-mediated signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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