Mutational analysis of Cys88 of Toll-like receptor 4 highlights the critical role of MD-2 in cell surface receptor expression

International Immunology

Volumn 21, Issue 8, 2009, Pages 925-934

  Nishitani, Chiaki ^a,b   Takahashi, Motoko ^a,b   Mitsuzawa, Hiroaki ^a,b   Shimizu, Takeyuki ^a,b   Ariki, Shigeru ^a,b   Matsushima, Norio ^c   Kuroki, Yoshio ^a,b  

^a SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^c SAPPORO MEDICAL UNIVERSITY   (Japan)

Author keywords

Innate immunity; LPS; MD 2; N linked glycosylation; Toll like receptor

Indexed keywords

ALANINE; CELL SURFACE RECEPTOR; COMPLEMENTARY DNA; CYSTEINE; GLYCOPEPTIDASE; GLYCOSIDASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 8; MANNOSE; MANNOSIDASE INHIBITOR; PROTEIN MD 2; TOLL LIKE RECEPTOR 4;

AMINO ACID SUBSTITUTION; ARTICLE; BIOTINYLATION; CONTROLLED STUDY; GENE EXPRESSION; GENETIC TRANSFECTION; GLYCOSYLATION; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOPRECIPITATION; KIDNEY CELL; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; WILD TYPE;

CELL LINE; CYSTEINE; DNA MUTATIONAL ANALYSIS; GLYCOSYLATION; HUMANS; LYMPHOCYTE ANTIGEN 96; MUTAGENESIS, SITE-DIRECTED; POLYSACCHARIDES; TOLL-LIKE RECEPTOR 4;

EID: 70349506775     PISSN: 09538178     EISSN: 14602377     Source Type: Journal    
DOI: 10.1093/intimm/dxp059     Document Type: Article

References (23)

1. Hoffmann, J. A., Kafatos, F. C., Janeway, C. A. and Ezekowitz, R. A. 1999. Phylogenetic perspectives in innate immunity. Science 284:1313.
2. Aderem, A. and Ulevitch, R. J. 2000. Toll-like receptors in the induction of the innate-immune response. Nature 406:782.
3. Chow, J. C., Young, D. W., Golenbock, D. T., Christ, W. J. and Gusovsky, F. 1999. Toll-like receptor-4 mediates lipopolysaccha-ride-induced signal transduction. J. Biol. Chem. 274:10689.
4. Shimazu, R., Akashi, S., Ogata, H. et al. 1999. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189:1777.
5. Wright, S. D., Ramos, R. A., Tobias, P. S., Ulevitch, R. J. and Mathison, J. C. 1990. CD14, a receptoe for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249:1431.
6. Schumann, R. R., Leong, S. R., Flaggs, G. W. et al. 1990. Structure and function of lipopolysaccharide binding protein. Science 249:1429.
7. Jiang, Q., Akashi, S., Miyake, K. and Petty, H. R. 2000. Lipopolysaccharide induces physical proximity between CD14 and toll-like receptor 4 (TLR4) prior to nuclear translocation of NF-kappa B. J. Immunol. 165:3541.
8. Poltorak, A., He, X., Smirnova, I. et al. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in TIr4 gene. Science 282:2085.
9. da, Silva, Correia, J. and Ulevitch, R. J. 2002. MD-2 and TLR4 N linked glycosylations are important for a functional lipopolysac-charide receptor. J. Biol. Chem. 277:1845.
10. Ohnishi, T., Muroi, M. and Tanamoto, K. 2003. MD-2 is necessary for the toll-like receptor 4 protein to undergo glycosylation essential for its translocation to the cell surface. Clin. Diagn. Lab. Immunol. 10:405.
11. Fujimoto, T., Yamazaki, S., Eto-Kimura, A., Takeshige, K. and Muta, T. 2004. The amino-terminal region of Toll-like receptor 4 is essential for binding to MD-2 and receptor translocation to the cell surface. J. Biol. Chem. 279:47431.
12. Nishitani, C., Mitsuzawa, H., Sano, H., Shimizu, T., Matsushima, N. and Kuroki, Y. 2006. Toll-like receptor 4 region Glu24-Lys47 is a site for MD-2 binding: Importance of Cys29 and Cys40. J. Biol. Chem. 281:38322.
13. Nagai, Y., Akashi, S., Nagafuku, M. et al. 2002. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat. Immunol. 3:667.
14. Randow, F. and Seed, B. 2001. Endoplastic reticulum chaperone gp96 is required for innate immunity but not cell viability. Nat. Cell. Biol. 3:891.
15. Wakabayashi, Y., Kobayashi, M., Akashi-Takamura, S. et al. 2006. A protein associated with Toll-like receptor 4 (PRAT4A) regulates cell surface expression of TLR4. J. Immunol. 177:1772.
16. Gioannini, T. L., Teghanemt, A., Zhang, D. et al. 2004. Isolation of an endotoxin-MD-2 complex that produces Toll-like receptor 4-dependent cell activation at picomolar concentrations. Proc. Natl Acad. Sci. USA 101:4186.
17. Jia, H. P., Kline, J. N., Penisten, A. et al. 2004. Endotoxin responsiveness of human airway epithelia is limited by Iow expression of MD-2. Am. J. Physiol. Lung Cell. Mol. Physiol. 287:L428.
18. Kennedy, M. N., Mullen, G. E., Leifer, C. A. et al. 2004. A complex of soluble MD-2 and lipopolysaccharide serves as an activating ligand for Toll-like receptor 4. J. Biol. Chem. 279:34698.
19. Kim, M. H., Park, B. S., Kim, J. et al. 2007. Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritorian Cell 130:906.
20. Nishitani, C., Mitsuzawa, H., Hyakushima, N., Sano, H., Matsushima, N. and Kuroki, Y. 2005. The Toll-like receptor 4 region Glu24-Pro34 is critical for interaction with MD-2. Biochem. Biophys. Res. Commun. 328:586.
21. Mitsuzawa, H., Wada, I., Sano, H. et al. 2001. Extracellular Toll-like receptor 2 region containing Ser40-IIe64 but not Cys30-Ser39 is critical for the recognition of Staphylococcus aureus peptidoglycan. J. Biol. Chem. 276:41350.
22. Saitoh, S. and Miyake, K. 2006. Mechanism regulating cell surface expression and activation of Toll-like receptor 4. Chem. Rec. 6:311.
23. Takahashi, K., Shibata, T., Akahsi-Takamura, S. et al. 2007. A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses. J. Exp. Med. 204:2963.