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[资源] 2011年诺奖得主论文赏析(转自丁香园)

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发布日期：2011-10-03 19:06 文章来源：丁香园
点击次数：2335

Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M,Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B. Defective LPSsignaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene. Science.1998;282:2085-2088.

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作者: Poltorak, A (Poltorak, A); He, XL (He, XL); Smirnova, I (Smirnova, I); Liu, MY (Liu, MY); Van Huffel, C (Van Huffel, C); Du, X (Du, X); Birdwell, D (Birdwell, D); Alejos, E (Alejos, E); Silva, M (Silva, M); Galanos, C (Galanos, C); Freudenberg, M (Freudenberg, M); Ricciardi-Castagnoli, P (Ricciardi-Castagnoli, P); Layton, B (Layton, B); Beutler, B (Beutler, B)

来源出版物: SCIENCE 卷: 282 期: 5396 页: 2085-2088 DOI: 10.1126/science.282.5396.2085 出版年: DEC 11 1998

被引频次: 3,730 (来自 Web of Science)

引用的参考文献: 34

摘要: Mutations of the gene Lps selectively impede Lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susceptible to Gram-negative infection. The codominant Lps(d) allele of C3H/HeJ mice was shown to correspond to a missense mutation in the third exon of the Toll-Like receptor-4 gene (Tlr4), predicted to replace proline with histidine at position 712 of the polypeptide chain. C57BL/10ScCr mice are homozygous for a null mutation of Tlr4, Thus, the mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasm a mem bra ne. Destructive mutations of Tlr4 predispose to the development of Gram-negative sepsis, Leaving most aspects of immune function intact.

文献类型: Article

语种: English

KeyWords Plus: LIPOPOLYSACCHARIDE BINDING-PROTEIN; TUMOR NECROSIS FACTOR; C-JUN; ENDOTOXIN; DROSOPHILA; CELLS; TOLL; CD14; 18-WHEELER; CACHECTIN

通讯作者地址: Beutler, B (通讯作者),Univ Texas, SW Med Ctr, Howard Hughes Med Inst, 5323 Harry Hines Blvd, Dallas, TX 75235 USA

地址:

1. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75235 USA

2. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA

3. CNR, Cellular & Mol Pharmacol Ctr, I-20133 Milan, Italy

4. Max Planck Inst Immunbiol, D-7800 Freiburg, Germany

Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatorygene cassette sp?tzle/Toll/cactus controls the potent antifungal response in drosophilaadults. Cell. 1996;86:973-983.

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作者: Lemaitre, B (Lemaitre, B); Nicolas, E (Nicolas, E); Michaut, L (Michaut, L); Reichhart, JM (Reichhart, JM); Hoffmann, JA (Hoffmann, JA)

来源出版物: CELL 卷: 86 期: 6 页: 973-983 DOI: 10.1016/S0092-8674(00)80172-5 出版年: SEP 20 1996

被引频次: 1,520 (来自 Web of Science)

引用的参考文献: 55

摘要: The cytokine-induced activation cascade of NF-KB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/1-kappa B, and dorsal/NF-kappa B). Here we demonstrate that these parallels extend to the immune response of Drosophila. In particular, the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand, spatzle, control expression of the antifungal peptide gene drosomycin in adults. We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways.

文献类型: Article

语种: English

KeyWords Plus: DORSAL-VENTRAL PATTERN; NF-KAPPA-B; SIGNAL-TRANSDUCTION PATHWAY; INSECT IMMUNITY; INNATE IMMUNITY; SERINE PROTEASE; EMBRYONIC POLARITY; IL-1 RECEPTOR; HOST-DEFENSE; TOLL GENE

通讯作者地址: Lemaitre, B (通讯作者),INST BIOL MOL & CELLULAIRE,UPR 9022 CNRS,15 RUE RENE DESCARTES,F-67084 STRASBOURG,FRANCE

Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs ofmice. J. Exp. Med. 1973;137:1142-1162.

Steinman RM, Witmer MD. Lymphoid dendritic cells are potent stimulators of the primarymixed leukocyte reaction in mice. Proc Natl Acad Sci USA 1978;75:5132-5136.

Schuler G, Steinman RM. Murine epidermal Langerhans cells mature into potentimmunostimulatory dendritic cells in vitro. J Exp Med 1985;161:526-546.

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