The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article
Right arrow Full Text
Right arrow Full Text (PDF, 141K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shimazu, R.
Right arrow Articles by Kimoto, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shimazu, R.
Right arrow Articles by Kimoto, M.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1999/6/1777/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 11, June 7, 1999 1777-1782


Articles

MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4

Rintaro Shimazu, Sachiko Akashi, Hirotaka Ogata, Yoshinori Nagai, Kenji Fukudome, Kensuke Miyake, and Masao Kimoto

From the Department of Immunology, Saga Medical School, Saga, Japan

Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila Toll, a leucine-rich repeat molecule that can trigger innate responses against pathogens. The TLR4 gene has recently been shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS. However, transfection of TLR4 does not confer LPS responsiveness on a recipient cell line, suggesting a requirement for an additional molecule. Here, we report that a novel molecule, MD-2, is requisite for LPS signaling of TLR4. MD-2 is physically associated with TLR4 on the cell surface and confers responsiveness to LPS. MD-2 is thus a link between TLR4 and LPS signaling. Identification of this new receptor complex has potential implications for understanding host defense, as well as pathophysiologic, mechanisms.

Key Words: leucine-rich repeat • RP105 • MD-1 • nuclear factor {kappa}B • signaling


Address correspondence to Kensuke Miyake, Department of Immunology, Saga Medical School, Nabeshima, Saga 849-8501, Japan. Phone: 81-952-34-2256; Fax: 81-952-34-2049; E-mail: miyake{at}post.saga-med.ac.jp

R. Shimazu and S. Akashi contributed equally to this study.

Abbreviations used: GAPDH, glyceraldehyde-3-phosphate dehydrogenase; LRR, leucine-rich repeat; NF, nuclear factor; RT, reverse transcriptase; TLR, Toll-like receptor.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS