MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4
Autor: | Kenji Fukudome, Kensuke Miyake, Masao Kimoto, Hirotaka Ogata, Yoshinori Nagai, Rintaro Shimazu, Sachiko Akashi |
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Rok vydání: | 1999 |
Předmět: |
Lipopolysaccharides
Lymphocyte antigen 96 Receptor complex DNA Complementary Molecular Sequence Data Immunology Lymphocyte Antigen 96 Receptors Cell Surface Biology Transfection Cell Line Mice Animals Drosophila Proteins Humans Immunology and Allergy RP105 RNA Messenger Receptor Mice Inbred C3H Toll-like receptor Membrane Glycoproteins Base Sequence Sequence Homology Amino Acid Toll-Like Receptors NF-kappa B Articles NFKB1 Molecular biology leucine-rich repeat Mice Inbred C57BL Toll-Like Receptor 4 MD-1 Antigens Surface TLR4 lipids (amino acids peptides and proteins) Signal transduction signaling nuclear factor κB Signal Transduction |
Zdroj: | The Journal of Experimental Medicine |
ISSN: | 1540-9538 0022-1007 |
DOI: | 10.1084/jem.189.11.1777 |
Popis: | 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. |
Databáze: | OpenAIRE |
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