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211.
Specks U Fass DN Finkielman JD Hummel AM Viss MA Litwiller RD McDonald CJ 《Journal of biochemistry》2007,141(1):101-112
Proteinase 3 (PR3) is a neutral serine protease stored in neutrophil granules. It has substantial sequence homology with elastase, cathepsin G and azurocidin. PR3 is the target antigen for autoantibodies (ANCA) in Wegener's granulomatosis, a necrotizing vasculitis syndrome. ANCA have been implicated in the pathogenesis of this disease. PR3 has two potential Asn-linked glycosylation sites. This study was designed to determine the occupancy of these glycosylation sites, and to evaluate their effect on enzymatic function, intracellular processing, targeting to granules and recognition by ANCA. We found that glycosylation occurs at both sites in native neutrophil PR3 and in wild type recombinant PR3 (rPR3) expressed in HMC-1 cells. Using glycosylation deficient rPR3 mutants we found that glycosylation at Asn-147, but not at Asn-102, is critical for thermal stability, and for optimal hydrolytic activity of PR3. Efficient amino-terminal proteolytic processing of rPR3 is dependent on glycosylation at Asn-102. Targeting to granules is not dependent on glycosylation, but unglycosylated rPR3 gets secreted preferentially into media supernatants. Finally, a capture ELISA for ANCA detection, using rPR3 glycosylation variants as target antigens, reveals that in about 20% of patients, epitope recognition by ANCA is affected by the glycosylation status of PR3. 相似文献
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CD83 expression in sea bream macrophages is a marker for the LPS-induced inflammatory response 总被引:1,自引:1,他引:0
Doñate C Roher N Balasch JC Ribas L Goetz FW Planas JV Tort L MacKenzie S 《Fish & shellfish immunology》2007,23(4):877-885
CD83, a cell surface membrane glycoprotein member of the Ig superfamily which is commonly used as standard surface marker for dendritic cells, was cloned from gilthead sea bream macrophages using degenerate primers against conserved motifs of known CD83 sequences. The obtained cDNA contains an open reading frame of 669 nucleotides that translate into a 222 amino acid putative peptide. The deduced protein sequence shows conservation of features shared by vertebrate CD83 and multiple alignment with fish CD83 sequences reveals high homology. In cultured sea bream macrophages CD83 mRNA expression was significantly enhanced in a dose- and time-dependent fashion after stimulation with Escherichia coli LPS. These results indicate that in fish, macrophages express high levels of CD83 mRNA after LPS exposure and CD83 is therefore a good marker for activated mature myeloid cells in fish. 相似文献
214.
Graeme C. Hays Helen Bailey Steven J. Bograd W. Don Bowen Claudio Campagna Ruth H. Carmichael Paolo Casale Andre Chiaradia Daniel P. Costa Eduardo Cuevas P.J. Nico de Bruyn Maria P. Dias Carlos M. Duarte Daniel C. Dunn Peter H. Dutton Nicole Esteban Ari Friedlaender Kimberly T. Goetz Ana M.M. Sequeira 《Trends in ecology & evolution》2019,34(5):459-473
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Olena Andrukhova Alina Smorodchenko Monika Egerbacher Carmen Streicher Ute Zeitz Regina Goetz Victoria Shalhoub Moosa Mohammadi Elena E Pohl Beate Lanske Reinhold G Erben 《The EMBO journal》2014,33(3):229-246
αKlotho is thought to activate the epithelial calcium channel Transient Receptor Potential Vanilloid‐5 (TRPV5) in distal renal tubules through its putative glucuronidase/sialidase activity, thereby preventing renal calcium loss. However, αKlotho also functions as the obligatory co‐receptor for fibroblast growth factor‐23 (FGF23), a bone‐derived phosphaturic hormone. Here, we show that renal calcium reabsorption and renal membrane abundance of TRPV5 are reduced in Fgf23 knockout mice, similar to what is seen in αKlotho knockout mice. We further demonstrate that αKlotho neither co‐localizes with TRPV5 nor is regulated by FGF23. Rather, apical membrane abundance of TRPV5 in renal distal tubules and thus renal calcium reabsorption are regulated by FGF23, which binds the FGF receptor‐αKlotho complex and activates a signaling cascade involving ERK1/2, SGK1, and WNK4. Our data thereby identify FGF23, not αKlotho, as a calcium‐conserving hormone in the kidney. 相似文献
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Chi-Ping Day John Carter Zoe Weaver Ohler Carrie Bonomi Rajaa El Meskini Philip Martin Cari Graff-Cherry Lionel Feigenbaum Thomas Tüting Terry Van Dyke Melinda Hollingshead Glenn Merlino 《PloS one》2014,9(11)
Preclinical therapeutic assessment currently relies on the growth response of established human cell lines xenografted into immunocompromised mice, a strategy that is generally not predictive of clinical outcomes. Immunocompetent genetically engineered mouse (GEM)-derived tumor allograft models offer highly tractable preclinical alternatives and facilitate analysis of clinically promising immunomodulatory agents. Imageable reporters are essential for accurately tracking tumor growth and response, particularly for metastases. Unfortunately, reporters such as luciferase and GFP are foreign antigens in immunocompetent mice, potentially hindering tumor growth and confounding therapeutic responses. Here we assessed the value of reporter-tolerized GEMs as allograft recipients by targeting minimal expression of a luciferase-GFP fusion reporter to the anterior pituitary gland (dubbed the “Glowing Head” or GH mouse). The luciferase-GFP reporter expressed in tumor cells induced adverse immune responses in wildtype mouse, but not in GH mouse, as transplantation hosts. The antigenicity of optical reporters resulted in a decrease in both the growth and metastatic potential of the labeled tumor in wildtype mice as compared to the GH mice. Moreover, reporter expression can also alter the tumor response to chemotherapy or targeted therapy in a context-dependent manner. Thus the GH mice and experimental approaches vetted herein provide concept validation and a strategy for effective, reproducible preclinical evaluation of growth and response kinetics for traceable tumors. 相似文献
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Yikyung Park Patricia Hartge Steven C. Moore Cari M. Kitahara Albert R. Hollenbeck Amy Berrington de Gonzalez 《PloS one》2012,7(11)