Nat Immunol. 2003 Nov;4(11):1144-50. Epub 2003 Oct 12.

TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway.

Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, Kaisho T, Takeuchi O, Takeda K, Akira S.

Source

Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita Osaka 565-0871, Japan.

Abstract

Recognition of pathogens by Toll-like receptors (TLRs) triggers innate immune responses through signaling pathways mediated by Toll-interleukin 1 receptor (TIR) domain-containing adaptors such as MyD88, TIRAP and TRIF. MyD88 is a common adaptor that is essential for proinflammatory cytokine production, whereas TRIF mediates the MyD88-independent pathway from TLR3 and TLR4. Here we have identified a fourth TIR domain-containing adaptor, TRIF-related adaptor molecule (TRAM), and analyzed its physiological function by gene targeting. TRAM-deficient mice showed defects in cytokine production in response to the TLR4 ligand, but not to other TLR ligands. TLR4- but not TLR3-mediated MyD88-independent interferon-beta production and activation of signaling cascades were abolished in TRAM-deficient cells. Thus, TRAM provides specificity for the MyD88-independent component of TLR4 signaling.

PMID:: 14556004; [PubMed - indexed for MEDLINE]

Free full text

Publication Types, MeSH Terms, Substances, Secondary Source ID

Publication Types

Research Support, Non-U.S. Gov't

MeSH Terms

Substances

Secondary Source ID

GENBANK/AY232653

LinkOut - more resources

Full Text Sources

Other Literature Sources

Highlights from Nature Reviews Immunology - Nature Publishing Group

Molecular Biology Databases

KOMP Repository

Miscellaneous

Supplemental Content

Save items

Related citations in PubMed

Review Microbial recognition by Toll-like receptors. [J Dermatol Sci. 2004]
Review Microbial recognition by Toll-like receptors.
Takeda K, Akira S. J Dermatol Sci. 2004 Apr; 34(2):73-82.
Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. [Science. 2003]
Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway.
Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K, et al. Science. 2003 Aug 1; 301(5633):640-3. Epub 2003 Jul 10.
Cutting edge: TNFR-associated factor (TRAF) 6 is essential for MyD88-dependent pathway but not toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta (TRIF)-dependent pathway in TLR signaling. [J Immunol. 2004]
Cutting edge: TNFR-associated factor (TRAF) 6 is essential for MyD88-dependent pathway but not toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta (TRIF)-dependent pathway in TLR signaling.
Gohda J, Matsumura T, Inoue J. J Immunol. 2004 Sep 1; 173(5):2913-7.
Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. [Nature. 2002]
Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4.
Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, Hoshino K, Takeuchi O, Kobayashi M, Fujita T, et al. Nature. 2002 Nov 21; 420(6913):324-9.
Review TIR domain-containing adaptors define the specificity of TLR signaling. [Mol Immunol. 2004]
Review TIR domain-containing adaptors define the specificity of TLR signaling.
Yamamoto M, Takeda K, Akira S. Mol Immunol. 2004 Feb; 40(12):861-8.

See reviews... See all...

Cited by over 100 PubMed Central articles

Inefficient TLR4/MD-2 Heterotetramerization by Monophosphoryl Lipid A. [PLoS One. 2013]
Inefficient TLR4/MD-2 Heterotetramerization by Monophosphoryl Lipid A.
Casella CR, Mitchell TC. PLoS One. 2013; 8(4):e62622. Epub 2013 Apr 26.
Liposomal Lipopolysaccharide Initiates TRIF-Dependent Signaling Pathway Independent of CD14. [PLoS One. 2013]
Liposomal Lipopolysaccharide Initiates TRIF-Dependent Signaling Pathway Independent of CD14.
Watanabe S, Kumazawa Y, Inoue J. PLoS One. 2013; 8(4):e60078. Epub 2013 Apr 2.
Suppression of TLR signaling by targeting TIR domain-containing proteins. [Curr Protein Pept Sci. 2012]
Suppression of TLR signaling by targeting TIR domain-containing proteins.
Fekonja O, Avbelj M, Jerala R. Curr Protein Pept Sci. 2012 Dec; 13(8):776-88.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
BioSystems
Pathways and biological systems (BioSystems) that cite the current articles. Citations are from the BioSystems source databases (KEGG and BioCyc).
Gene
Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
Gene (GeneRIF)
Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.
Gene (OMIM)
Gene records associated with Online Mendelian Inheritance in Man (OMIM) records that cite the current articles in their reference lists.
HomoloGene
HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
Nucleotide
Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
Nucleotide (RefSeq)
NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
OMIM (calculated)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as references in the light bulb links within or in the citations at the end of the OMIM record. The references available through the light bulb link are collected using the PubMed related articles algorithm to identify records with similar terminology to the OMIM record.
OMIM (cited)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as reference cited at the end of the OMIM record.
Protein (RefSeq)
NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Taxonomy via GenBank
Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
UniGene
UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
Protein
Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
GEO Profiles
Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-indepen...
TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway.
Nat Immunol. 2003 Nov ;4(11):1144-50. Epub 2003 Oct 12 .

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: