Format

Send to

Choose Destination
J Biol Chem. 2004 Sep 3;279(36):37227-30. Epub 2004 Jul 9.

Mal interacts with tumor necrosis factor receptor-associated factor (TRAF)-6 to mediate NF-kappaB activation by toll-like receptor (TLR)-2 and TLR4.

Author information

1
Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria 3168, Australia. ashley.mansell@med.monash.edu.au

Abstract

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.

PMID:
15247281
DOI:
10.1074/jbc.C400289200
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center