Mal interacts with tumor necrosis factor receptor-associated factor (TRAF)-6 to mediate NF-kappaB 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.
Mesh Terms:
Cell Line, Humans, Membrane Glycoproteins, NF-kappa B, Protein Binding, Receptors, Cell Surface, Receptors, Interleukin-1, Signal Transduction, TNF Receptor-Associated Factor 6, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptors
Cell Line, Humans, Membrane Glycoproteins, NF-kappa B, Protein Binding, Receptors, Cell Surface, Receptors, Interleukin-1, Signal Transduction, TNF Receptor-Associated Factor 6, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptors
J. Biol. Chem.
Date: Sep. 03, 2004
PubMed ID: 15247281
View in: Pubmed Google Scholar
Download Curated Data For This Publication
142852
Switch View:
- Interactions 1