HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 6, 3423-3427, February 9, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/6/3423    most recent C600226200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sarkar, S. N. Articles by Sen, G. C. Search for Related Content PubMed PubMed Citation Articles by Sarkar, S. N. Articles by Sen, G. C. Social Bookmarking                      What's this?

Two Tyrosine Residues of Toll-like Receptor 3 Trigger Different Steps of NF-B Activation^*

From the Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195

Innate immune response to viral infection is often triggered by Toll-like receptor 3 (TLR3)-mediated signaling by double-stranded (ds) RNA, which culminates in the activation of the transcription factor NF-B and induction of NF-B-driven genes. We demonstrated that dsRNA-induced phosphorylation of two specific tyrosine residues, 759 and 858, of TLR3 was necessary and sufficient for complete activation of the NF-B pathway. When Tyr-759 of TLR3 was mutated, gene induction was inhibited, although NF-B was partially activated. It was released from IB and translocated to the nucleus but failed to bind to the B site of the target A20 gene promoter. This defect could be attributed to incomplete phosphorylation of the RelA (p65) subunit of NF-B, as revealed by two-dimensional gel analyses of p65, isolated from dsRNA-treated cells expressing either wild type TLR3 or the Tyr-759 Phe mutant TLR3. Thus, two phosphotyrosine residues of TLR3 activate two distinct pathways, one leading to NF-B release and the other leading to its phosphorylation.

Received for publication, August 24, 2006 , and in revised form, November 20, 2006.

^* This work was supported in part by National Institutes of Health Grants CA68782 and CA62220. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.

¹ To whom correspondence should be addressed: Dept. of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195. Tel.: 216-444-0636; Fax: 216-444-0513; E-mail: seng{at}ccf.org.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. West and B. Damania Upregulation of the TLR3 Pathway by Kaposi's Sarcoma-Associated Herpesvirus during Primary Infection J. Virol., June 1, 2008; 82(11): 5440 - 5449. [Abstract] [Full Text] [PDF]

				S. Fan, S. Chen, Y. Liu, Y. Lin, H. Liu, L. Guo, B. Lin, S. Huang, and A. Xu Zebrafish TRIF, a Golgi-Localized Protein, Participates in IFN Induction and NF-{kappa}B Activation J. Immunol., April 15, 2008; 180(8): 5373 - 5383. [Abstract] [Full Text] [PDF]

				F. F. Tuon, V. S. Amato, H. A. Bacha, T. AlMusawi, M. I. Duarte, and V. Amato Neto Toll-Like Receptors and Leishmaniasis Infect. Immun., March 1, 2008; 76(3): 866 - 872. [Full Text] [PDF]

				E. Vercammen, J. Staal, and R. Beyaert Sensing of Viral Infection and Activation of Innate Immunity by Toll-Like Receptor 3 Clin. Microbiol. Rev., January 1, 2008; 21(1): 13 - 25. [Abstract] [Full Text] [PDF]