Mal Interacts with Tumor Necrosis Factor Receptor-associated Factor (TRAF)-6 to mediate NF-κB Activation by Toll-like Receptor (TLR)-2 and TLR4
Copyright policy )Mal Interacts with Tumor Necrosis Factor Receptor-associated Factor (TRAF)-6 to mediate NF-κB Activation by Toll-like Receptor (TLR)-2 and TLR4
The Toll-interleukin-1 receptor domain-containing adapter Mal (MyD88 adapter-like protein) is involved in Toll-like receptor (TLR)-2 and TLR4 signal transduction. However, no studies have yet identified a function for Mal distinct from the related adapter MyD88. In this study, we have identified a putative TRAF6 interaction site in Mal but not in MyD88 and we demonstrate that Mal can be co-immunoprecipitated with TRAF6. Overexpression of MalE190A, which contains a mutation within the TRAF6-binding motif, failed to induce the expression of an NF-kappaB-dependent reporter gene, p65-mediated transactivation of gene expression, or activation of Jun N-terminal kinase or p42/p44 MAP kinase, which are induced with wild type Mal. MalE190A inhibited TLR2- and TLR4-mediated activation of NF-kappaB. These results identify a specific role for Mal in TLR-mediated signaling in regulating NF-kappaB-dependent gene transcription via its interaction with TRAF6.
- Cooperative Research Centre Australia
- Monash University Australia
- Trinity College Dublin Ireland
TNF Receptor-Associated Factor 6, Membrane Glycoproteins, Toll-Like Receptors, NF-kappa B, 610, Receptors, Interleukin-1, Receptors, Cell Surface, Biochemistry, Toll-Like Receptor 2, Cell Line, Toll-Like Receptor 4, Humans, Protein Binding, Signal Transduction
TNF Receptor-Associated Factor 6, Membrane Glycoproteins, Toll-Like Receptors, NF-kappa B, 610, Receptors, Interleukin-1, Receptors, Cell Surface, Biochemistry, Toll-Like Receptor 2, Cell Line, Toll-Like Receptor 4, Humans, Protein Binding, Signal Transduction
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