J Biol Chem. 2003 Feb 14;278(7):4393-6. Epub 2002 Dec 30.

Double-stranded RNA signaling by Toll-like receptor 3 requires specific tyrosine residues in its cytoplasmic domain.

Source

Department of Molecular Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Abstract

Double-stranded (ds) RNA, a common product of viral infection, can induce transcription of many cellular genes, including the 561 gene that encodes P56, a regulator of protein synthesis. Here, we report that induction of the 561 mRNA by exogenous dsRNA is mediated by Toll-like receptor 3 (TLR3), and it requires no new protein synthesis. Because gene induction by dsRNA is blocked by inhibitors of tyrosine kinases, we investigated the potential roles of the five tyrosine residues present in the cytoplasmic domain of TLR3 by their individual and combinatorial mutations. Transfection assays, using a reporter gene driven by the 561 promoter, identified specific tyrosine residues to be essential for TLR3 signaling. This conclusion was further validated in permanent cell lines expressing tyrosine-mutant TLR3 proteins; in some of these cell lines dsRNA failed to induce the 561 mRNA. Our results provide the first demonstration of the importance of TLR3 cytoplasmic tyrosine residues in dsRNA signaling.

PMID:: 12509442; [PubMed - indexed for MEDLINE]

Free full text

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

Research Support, U.S. Gov't, P.H.S.

MeSH Terms

Substances

Grant Support

LinkOut - more resources

Full Text Sources

Other Literature Sources

COS Scholar Universe

Molecular Biology Databases

Supplemental Content

Related citations

Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. [Biochem Biophys Res Commun. 2002]
Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling.
Matsumoto M, Kikkawa S, Kohase M, Miyake K, Seya T. Biochem Biophys Res Commun. 2002 May 24; 293(5):1364-9.
mRNA is an endogenous ligand for Toll-like receptor 3. [J Biol Chem. 2004]
mRNA is an endogenous ligand for Toll-like receptor 3.
Karikó K, Ni H, Capodici J, Lamphier M, Weissman D. J Biol Chem. 2004 Mar 26; 279(13):12542-50. Epub 2004 Jan 16.
Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling. [Nat Struct Mol Biol. 2004]
Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling.
Sarkar SN, Peters KL, Elco CP, Sakamoto S, Pal S, Sen GC. Nat Struct Mol Biol. 2004 Nov; 11(11):1060-7. Epub 2004 Oct 24.
Review Transcriptional signaling by double-stranded RNA: role of TLR3. [Cytokine Growth Factor Rev. 2005]
Review Transcriptional signaling by double-stranded RNA: role of TLR3.
Sen GC, Sarkar SN. Cytokine Growth Factor Rev. 2005 Feb; 16(1):1-14.
Review [Recognition of dsRNA by toll-like receptor 3]. [Uirusu. 2001]
Review [Recognition of dsRNA by toll-like receptor 3].
Matsumoto M, Seya T. Uirusu. 2001 Dec; 51(2):209-14.

See reviews... See all...

Cited by 13 PubMed Central articles

Mal connects TLR2 to PI3Kinase activation and phagocyte polarization. [EMBO J. 2009]
Mal connects TLR2 to PI3Kinase activation and phagocyte polarization.
Santos-Sierra S, Deshmukh SD, Kalnitski J, Küenzi P, Wymann MP, Golenbock DT, Henneke P. EMBO J. 2009 Jul 22; 28(14):2018-27. Epub 2009 Jul 2.
Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth. [Proc Natl Acad Sci U S A. 2009]
Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth.
Cho WG, Albuquerque RJ, Kleinman ME, Tarallo V, Greco A, Nozaki M, Green MG, Baffi JZ, Ambati BK, De Falco M, et al. Proc Natl Acad Sci U S A. 2009 Apr 28; 106(17):7137-42. Epub 2009 Apr 9.
Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice. [J Clin Invest. 2009]
Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice.
Judge AD, Robbins M, Tavakoli I, Levi J, Hu L, Fronda A, Ambegia E, McClintock K, MacLachlan I. J Clin Invest. 2009 Mar; 119(3):661-73. Epub 2009 Feb 23.

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.
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
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.
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 (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.
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.
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

Double-stranded RNA signaling by Toll-like receptor 3 requires specific tyrosine...
Double-stranded RNA signaling by Toll-like receptor 3 requires specific tyrosine residues in its cytoplasmic domain.
J Biol Chem. 2003 Feb 14 ;278(7):4393-6. Epub 2002 Dec 30 .

PubMed
Rabphilin dissociated from Rab3 promotes endocytosis through interaction with Ra...
Rabphilin dissociated from Rab3 promotes endocytosis through interaction with Rabaptin-5.
J Cell Sci. 2001 May ;114(Pt 9):1757-64.

PubMed
Idiopathic eosinophilic meningoencephalomyelitis following Well syndrome.
Idiopathic eosinophilic meningoencephalomyelitis following Well syndrome.
Neurology. 2009 Dec 8 ;73(23):2037-9.

PubMed
The accuracy and reliability of an infusion pump (STC-3121; Terumo Inst., Japan)...
The accuracy and reliability of an infusion pump (STC-3121; Terumo Inst., Japan) during hyperbaric oxygenation.
Anaesth Intensive Care. 2000 Feb ;28(1):68-71.

PubMed
Vagal tone as an indicator of treatment response in major depression.
Vagal tone as an indicator of treatment response in major depression.
Psychophysiology. 2002 Nov ;39(6):861-4.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Display Settings:

Send to: