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排序方式: 共有119条查询结果,搜索用时 359 毫秒
81.
Maja Kazazic Vibeke Bertelsen Ketil Winther Pedersen Tram Thu Vuong Michael Vibo Grandal Marianne Skeie Rødland Linton M. Traub Espen Stang Inger Helene Madshus 《Traffic (Copenhagen, Denmark)》2009,10(2):235-245
Epsin consists of an epsin NH2 -terminal homology domain that promotes interaction with phospholipids, several AP-2-binding sites, two clathrin-binding sequences and several Eps15 homology domain-binding motifs. Epsin additionally possesses ubiquitin-interacting motifs (UIMs) and has been demonstrated to bind ubiquitinated cargo. We therefore investigated whether epsin promoted clathrin-mediated endocytosis of the ubiquitinated EGF receptor (EGFR). By immunoprecipitation, we found that epsin 1 interacted with ubiquitinated EGFR and that functional UIMs were essential for complex formation. Furthermore, RNA interference-mediated knockdown of epsin 1 was found to inhibit internalization of the EGFR, while having no effect on endocytosis of the transferrin receptor. Additionally, upon knockdown of epsin 1, translocation of the EGFR to central parts of clathrin-coated pits was inhibited. This supports the contention that epsin 1 promotes endocytosis of the ubiquitinated EGFR. 相似文献
82.
Zhang W Yao J Pham V Whitney T Froese D Friesen A Stang L Xu C Shuaib A Diakur JM Haque W 《Bioorganic & medicinal chemistry letters》2004,14(18):4747-4750
The B(6) vitamers have been shown to display beneficial therapeutic effects in cardiovascular related disorders. The design of novel antiplatelet agents using pyridoxine as a template has led to the discovery of a class of novel cardio- and cerebro-protective agents. The present study describes the synthesis of several of these derivatives along with the antiplatelet and antiischemic activity of derivative 16. 相似文献
83.
Yong Qu Machteld C. Mok David W. S. Mok Jack R. Stang 《In vitro cellular & developmental biology. Plant》1988,24(5):471-476
Summary Anther culture of the Easter Lily (Lilium longiflorum; 2n=2x=24) was attempted in order to evaluate its potential in generating haploids for the production of hybrid cultivars.
The effects of genotype, temperature (low temperature treatment of buds and high temperature treatment of cultures), sucrose
concentration and growth regulators were tested. The most important factors for callus induction were the genotype and the
presence of 2,4-dichlorophenoxyacetic acid. Pre-treatments at low or high temperature had no apparent effect, while high sucrose
concentration was inhibitory. Callus was derived from 28 of the 108 genotypes tested and plants were regenerated. Phenotypic
variations were observed among these regenerants. Somatic chromosome numbers were determined in 42 plants derived from 10
donor genotypes. Thirteen plants were diploid and 29 were mixoploid with chromosome numbers ranging from 11 to 26. Four of
the mixoploid plants had a high proportion of cells with haploid chromosome numbers, particularly at early stages of development.
Meiosis was examined in plants with flower buds. Most plants had 12 bivalents at Metaphase I, but also aneuploids were observed.
Other irregularities included bridges and laggards at Anaphase I. The occurrence of high frequencies of haploid cells (up
to 80%) in root tips suggests that some plants may be of gametic origin.
Research was supported by the Easter Lily Research Foundation, the Ohio Floriculture Foundation, the Gloeckner Foundation
and the Oregon Agricultural Experiment Station (technical paper no. 8398). 相似文献
84.
The ability of particular cell surface glycoproteins to recycle and become
exposed to individual Golgi enzymes has been demonstrated. This study was
designed to determine whether endocytic trafficking includes significant
reentry into the overall oligosaccharide processing pathway. The Lec1
mutant of Chinese hamster ovary (CHO) cells lack N -
acetylglucosaminyltransferase I (GlcNAc-TI) activity resulting in surface
expression of incompletely processed Man5GlcNAc2 N -linked
oligosaccharides. An oligosaccharide tracer was created by exoglycosylation
of cell surface glycoproteins with purified porcine GlcNAc-TI and
UDP-[3H]GlcNAc. Upon reculturing, all cell surface glycoproteins that
acquired [3H]GlcNAc were acted upon by intracellular mannosidase II, the
next enzyme in the Golgi processing pathway of complex N -linked
oligosaccharides (t1/2= 3-4 h). That all radiolabeled cell surface
glycoproteins were included in this endocytic pathway indicates a common
intracellular compartment into which endocytosed cell surface glycoproteins
return. Significantly, no evidence was found for continued oligosaccharide
processing consistent with transit through the latter cisternae of the
Golgi apparatus. These data indicate that, although recycling plasma
membrane glycoproteins can be reexposed to individual Golgi-derived
enzymes, significant reentry into the overall contiguous processing pathway
is not evident.
相似文献
85.
The role of site-specific N-glycosylation in secretion of soluble forms of rabies virus glycoprotein 总被引:1,自引:1,他引:0
Wojczyk BS; Stwora-Wojczyk M; Shakin-Eshleman S; Wunner WH; Spitalnik SL 《Glycobiology》1998,8(2):121-130
Rabies virus glycoprotein is important in the biology and pathogenesis of
neurotropic rabies virus infection. This transmembrane glycoprotein is the
only viral protein on the surface of virus particles, is the viral
attachment protein that facilitates virus uptake by the infected cell, and
is the target of the host humoral immune response to infection. The
extracellular domain of this glycoprotein has N- glycosylation sequons at
Asn37, Asn247, and Asn319. Appropriate glycosylation of these sequons is
important in the expression of the glycoprotein. Soluble forms of rabies
virus glycoprotein were constructed by insertion of a stop codon just
external to the transmembrane domain. Using site-directed mutagenesis and
expression in transfected eukaryotic cells, it was possible to compare the
effects of site-specific glycosylation on the cell-surface expression and
secretion of transmembrane and soluble forms, respectively, of the same
glycoprotein. These studies yielded the surprising finding that although
any of the three sequons permitted cell surface expression of full-length
rabies virus glycoprotein, only the N-glycan at Asn319 permitted secretion
of soluble rabies virus glycoprotein. Despite its biological and medical
importance, it has not yet been possible to determine the crystal structure
of the full-length transmembrane form of rabies virus glycoprotein which
contains heterogeneous oligosaccharides. The current studies demonstrate
that a soluble form of rabies virus glycoprotein containing only one sequon
at Asn319 is efficiently secreted in the presence of the N-glycan
processing inhibitor 1-deoxymannojirimycin. Thus, it is possible to purify
a conformationally relevant form of rabies virus glycoprotein that contains
only one N-glycan with a substantial reduction in its microheterogeneity.
This form of the glycoprotein may be particularly useful for future studies
aimed at elucidating the three-dimensional structure of this important
glycoprotein.
相似文献
86.
A combination of two antibodies recognizing non‐overlapping epitopes of HER2 induces kinase activity‐dependent internalization of HER2
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Monika Szymanska Anne M. Fosdahl Filip Nikolaysen Mikkel W. Pedersen Michael M. Grandal Espen Stang Vibeke Bertelsen 《Journal of cellular and molecular medicine》2016,20(10):1999-2010
The human epidermal growth factor receptor 2 (HER2/ErbB2) is overexpressed in a number of human cancers. HER2 is the preferred heterodimerization partner for other epidermal growth factor receptor (EGFR) family members and is considered to be resistant to endocytic down‐regulation, properties which both contribute to the high oncogenic potential of HER2. Antibodies targeting members of the EGFR family are powerful tools in cancer treatment and can function by blocking ligand binding, preventing receptor dimerization, inhibiting receptor activation and/or inducing receptor internalization and degradation. With respect to antibody‐induced endocytosis of HER2, various results are reported, and the effect seems to depend on the HER2 expression level and whether antibodies are given as individual antibodies or as mixtures of two or more. In this study, the effect of a mixture of two monoclonal antibodies against non‐overlapping epitopes of HER2 was investigated with respect to localization and stability of HER2. Individual antibodies had limited effect, but the combination of antibodies induced internalization and degradation of HER2 by multiple endocytic pathways. In addition, HER2 was phosphorylated and ubiquitinated upon incubation with the antibody combination, and the HER2 kinase activity was found to be instrumental in antibody‐induced HER2 down‐regulation. 相似文献
87.
Corn samples were collected in 1999 from three departments of Entre Réos province, Argentina, and were surveyed for mould
contamination and natural occurrence ofFusarium mycotoxins, ochratoxin A and aflatoxins.Fusarium verticillioides was the most prevalent fungal species recorded at all departments. Zearalenone, deoxynivalenol and ochratoxin A were not
found in any samples. Only one of the 52 corn samples analysed was contaminated with aflatoxin B1 (17 μg/kg). Fumonisin B1 was found in 58 % of samples (range of positive samples: 47– 3,347 μg/kg), fumonisin B2 in 33.0 % (range of positive samples: 23–537 μg/kg) and fumonisin B3 in 25.0 % (range of positive samples: 24–287 μg/kg) of them. This is the first report on the natural occurrence of mycotoxins
in corn from Entre Ríos province, Argentina. Levels of fumonisins were lower than detected in other Argentinian provinces. 相似文献
88.
Geldanamycin-induced down-regulation of ErbB2 from the plasma membrane is clathrin dependent but proteasomal activity independent 总被引:1,自引:0,他引:1
ErbB2, a member of the epidermal growth factor receptor family, is overexpressed in a number of human cancers. In contrast to the epidermal growth factor receptor, ErbB2 is normally endocytosis resistant. However, ErbB2 can be down-regulated by inhibitors of heat shock protein 90, such as geldanamycin. We now show that geldanamycin induces endocytosis and lysosomal degradation of full-length ErbB2. We further report that the endocytosis of ErbB2 is dynamin and clathrin dependent. When ErbB2 was retained at the plasma membrane due to knockdown of clathrin heavy chain, the intracellular part of ErbB2 was degraded in a proteasomal manner. However, our data strongly suggest that proteasomal activity is not required for geldanamycin-induced endocytosis of ErbB2 in SKBr3 cells. Interestingly, however, proteasomal inhibitors retarded degradation of ErbB2, and electron microscopy analysis strongly suggested that proteasomal activity is required to sort internalized ErbB2 to lysosomes. Because geldanamycin derivatives and inhibitors of proteasomal activity are both used in experimental cancer treatment, knowledge of molecular mechanisms involved in geldanamycin-induced down-regulation of ErbB2 is important for future design of cancer treatment. 相似文献
89.
Despite the recent introduction of biological response modifiers and potent new small-molecule antirheumatic drugs, the efficacy of methotrexate is nearly unsurpassed in the treatment of inflammatory arthritis. Although methotrexate was first introduced as an antiproliferative agent that inhibits the synthesis of purines and pyrimidines for the therapy of malignancies, it is now clear that many of the anti-inflammatory effects of methotrexate are mediated by adenosine. This nucleoside, acting at one or more of its receptors, is a potent endogenous anti-inflammatory mediator. In confirmation of this mechanism of action, recent studies in both animals and patients suggest that adenosine-receptor antagonists, among which is caffeine, reverse or prevent the anti-inflammatory effects of methotrexate. 相似文献
90.
Carsten Rusner Britton Trabert Alexander Katalinic Joachim Kieschke Katharina Emrich Andreas Stang 《Cancer epidemiology》2013,37(4):370-373
BackgroundMalignant gonadal (GGCT) and extragonal germ cell tumors [GCT (EGCT)] are thought to originate from primordial germ cells. In contrast to well reported population-based data of GGCTs in males, analyses of GGCTs in females and EGCTs in both sexes remain limited.MethodsIn a pooling project of nine population-based cancer registries in Germany for the years 1998–2008, 16,883 malignant GCTs and their topographical sites were identified using ICD-O morphology and topography for persons aged 15 years and older. We estimated age-specific and age-standardized incidence rates.ResultsAmong males, the incidence of testicular GCTs increased over time. In contrast, there was no increase in the incidence of EGCTs. Among females, rates of ovarian GCTs were stable, while rates of EGCTs declined over time. The most frequent extragonadal sites were mediastinum among males and placenta among females.ConclusionsOur results underline different incidence trends and distinct age-specific incidence patterns of malignant GGCTs and EGCTs, as reported recently by several population-based registries. The differences suggest that GGCT and EGCT may have different etiologies. 相似文献