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Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus 总被引:1,自引:0,他引:1
Nierman WC Pain A Anderson MJ Wortman JR Kim HS Arroyo J Berriman M Abe K Archer DB Bermejo C Bennett J Bowyer P Chen D Collins M Coulsen R Davies R Dyer PS Farman M Fedorova N Fedorova N Feldblyum TV Fischer R Fosker N Fraser A García JL García MJ Goble A Goldman GH Gomi K Griffith-Jones S Gwilliam R Haas B Haas H Harris D Horiuchi H Huang J Humphray S Jiménez J Keller N Khouri H Kitamoto K Kobayashi T Konzack S Kulkarni R Kumagai T Lafon A Lafton A Latgé JP Li W Lord A Lu C Majoros WH May GS 《Nature》2005,438(7071):1151-1156
Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus. 相似文献
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Zeng X Tamai K Doble B Li S Huang H Habas R Okamura H Woodgett J He X 《Nature》2005,438(7069):873-877
Signalling by the Wnt family of secreted lipoproteins has essential functions in development and disease. The canonical Wnt/beta-catenin pathway requires a single-span transmembrane receptor, low-density lipoprotein (LDL)-receptor-related protein 6 (LRP6), whose phosphorylation at multiple PPPSP motifs is induced upon stimulation by Wnt and is critical for signal transduction. The kinase responsible for LRP6 phosphorylation has not been identified. Here we provide biochemical and genetic evidence for a 'dual-kinase' mechanism for LRP6 phosphorylation and activation. Glycogen synthase kinase 3 (GSK3), which is known for its inhibitory role in Wnt signalling through the promotion of beta-catenin phosphorylation and degradation, mediates the phosphorylation and activation of LRP6. We show that Wnt induces sequential phosphorylation of LRP6 by GSK3 and casein kinase 1, and this dual phosphorylation promotes the engagement of LRP6 with the scaffolding protein Axin. We show further that a membrane-associated form of GSK3, in contrast with cytosolic GSK3, stimulates Wnt signalling and Xenopus axis duplication. Our results identify two key kinases mediating Wnt co-receptor activation, reveal an unexpected and intricate logic of Wnt/beta-catenin signalling, and illustrate GSK3 as a genuine switch that dictates both on and off states of a pivotal regulatory pathway. 相似文献