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141.
Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP 总被引:3,自引:0,他引:3
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Galic S Klingler-Hoffmann M Fodero-Tavoletti MT Puryer MA Meng TC Tonks NK Tiganis T 《Molecular and cellular biology》2003,23(6):2096-2108
The human protein tyrosine phosphatase TCPTP exists as two forms: an endoplasmic reticulum-targeted 48-kDa form (TC48) and a nuclear 45-kDa form (TC45). Although targeted to the nucleus, TC45 can exit in response to specific stimuli to dephosphorylate cytoplasmic substrates. In this study, we investigated the downregulation of insulin receptor (IR) signaling by TCPTP. In response to insulin stimulation, the TC48-D182A and TC45-D182A "substrate-trapping" mutants formed stable complexes with the endogenous tyrosine-phosphorylated IR beta-subunit in 293 cells. Moreover, in response to insulin stimulation, the TC45-D182A mutant accumulated in the cytoplasm of cells overexpressing the IR and in part colocalized with the IR beta-subunit at the cell periphery. These results indicate that the IR may serve as a cellular substrate for both TC48 and TC45. In immortalized TCPTP(-/-) murine embryo fibroblasts, insulin-induced IR beta-subunit tyrosine phosphorylation and protein kinase PKB/Akt activation were enhanced relative to the values in TCPTP(+/+) cells. Importantly, the expression of TC45 or TC48 to physiological levels suppressed the enhanced insulin-induced signaling in TCPTP(-/-) cells. These results indicate that the differentially localized variants of TCPTP may dephosphorylate the IR and downregulate insulin-induced signaling in vivo. 相似文献
142.
Zanotto C Elli V Basavecchia V Brivio A Paganini M Pinna D Vicenzi E De Giuli Morghen C Radaelli A 《FEMS immunology and medical microbiology》2003,35(1):59-65
Two different prime-boost immunization protocols were tested in rabbits and their immune response was evaluated and compared with the final aim of defining a vaccine strategy that might be able to protect non-human primates from infection with the pathogenic simian/human immunodeficiency virus, SHIV(89.6P). The two regimens were based on three priming immunizations with either an expression plasmid plus a fowlpox (FP) recombinant vector or with two FP recombinant vectors, each one expressing either the SIV(mac239) gag/pol or the HIV-1env(89.6P) genes. In both protocols, priming immunizations were followed by two boosts with SHIV-mimicking virus-like particles (VLP). A complete SHIV-specific response was observed in all animals. Interestingly, the DNA vaccine was three to 10 times more efficient than the FP recombinant in inducing an anti-gag humoral response. Real-time PCR confirmed the memory effect on T-cell subsets secreting interleukin-4 and interferon-gamma, as a consequence of stimulation of both arms of the immune system. Although both protocols were almost equally effective in eliciting homologous neutralizing antibodies and highlighted the efficacy of VLP administration for boosting, protocol A seemed to be more effective in promoting a balanced T-cell memory immune response and appears more promising for vaccine purposes. 相似文献
143.
We analysed the mycorrhizal types of two coastal Mediterranean plant communities. Plants belonging to 82 species of 46 families growing in two Mediterranean study sites located within a Regional Natural Park in Italy (Macchia Lucchese) and in a National Park in Croatia (Brijuni) were assessed for the type of their mycorrhizal associations. Mycorrhizas occurred in 83% and 90% of the plant species surveyed in Macchia Lucchese and in Brijuni, respectively. On the basis of macroscopic and microscopic characteristics, six different mycorrhizal types were found, and their co-occurrence in the same plant community showed the large mycorrhizal diversity in Mediterranean vegetation. Different occurrence patterns of mycorrhizal types have been recognised in diverse habitats within Macchia Lucchese, from sand dune plant communities to sclerophyllous woodland. Mycorrhizal type abundance calculated on a floristic basis was very different from that obtained using a vegetation cover index. 相似文献
144.
The nucleolus is a very dynamic structure able rapidly to adapt its activity to the cellular metabolic state. An interesting physiological model characterized by drastic modifications of cellular metabolism is represented by hibernating animals. In the present study we investigated the hepatocyte nuclei of euthermic and hibernating edible dormice (Glis glis) with the aim of revealing, by means of ultrastructural and immunocytochemical analyses, possible modifications of nucleolar components during hibernation. Our observations demonstrate that, in deep hibernation, nucleoli undergo structural and molecular modifications: (a) they show numerous nucleoplasmic invaginations and clumps of dense fibrillar component extend from the nucleolar surface; (b) they are frequently in contact with coiled bodies and fibro-granular material, two nuclear bodies usually occurring in the nucleoplasm; (c) the dense fibrillar component contains significant amounts of small nuclear ribonucleoproteins, splicing factors usually distributed in the nucleoplasm. Taken together, these results suggest that during hibernation complex relationships are established between the nucleolus and nucleoplasm, probably related to functional activities peculiar to this physiological phase. However, since no evident nucleolar modification was found in early hibernating dormice, it seems likely that the particular structural and molecular arrangement of nucleoli establishes progressively during hibernation, becoming evident only in the deepest phase, and then disappears upon arousal. 相似文献
145.
To evaluate the importance and fate of organic matter inputs in forested streams, we determined the litterfall inputs and
the benthic coarse particulate organic matter (CPOM) in one headwater stream flowing through a mixed deciduous forest, during
one year. Both vertical traps and the stream bottom were sampled monthly. The material collected was sorted into four main
categories: leaves, fruits and flowers, twigs and debris. Litter production was 715 g m−2 y−1 and seasonal, with 73% of the
annual total during October–December (autumn). Leaves comprised the largest litter component. Benthic organic matter was 1880
g m−2 y−1, and was also seasonal. Highest accumulation was attained in spring, and twigs and branches comprised the major
component.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
146.
Cláudio M. Gomes Alice Faria João C. Carita Joaquim Mendes Manuela Regalla Paula Chicau Harald Huber Karl O. Stetter M. Teixeira 《Journal of biological inorganic chemistry》1998,3(5):499-507
Seven-iron ferredoxins from the thermoacidophilic archaea Acidianus ambivalens, A. infernus, Metalosphaera prunae and Sulfolobus metallicus were extensively characterised, allowing study of their expression under aerobic and anaerobic growth conditions as well
as the putative role in thermal stability of a recently described zinc centre. The archaeon S. metallicus was found to express, under the same growth conditions, two ferredoxins in almost identical amounts, a novelty among Archaea. Most interestingly, these two ferredoxins differ at the N-terminal amino acid sequence in that one has a zinc binding motif
(FdA) and the other does not (FdB); in agreement with these findings, FdA contains a zinc ion and FdB does not. These two
ferredoxins have identical thermal stabilities, indicating that the zinc atom is not determinant in the protein thermostability.
Further, the presence of the additional zinc centre does not interfere with the redox properties of the iron-sulfur clusters
since their reduction potentials are almost identical. From the other three archaea, independently of the growth mode in respect
to oxygen, only a single zinc-containing ferredoxin was found. EPR studies on the purified proteins, both in the oxidised
and dithionite reduced states, allowed the identification of one [3Fe-4S]1+/0 centre and one [4Fe-4S]2+/1+ centre in all proteins studied. The complete sequence of A. ambivalens ferredoxin is reported. Together with the data gathered in this study, the properties of the seven-iron ferredoxins from
Sulfolobales so far known are re-discussed.
Received: 10 June 1998 / Accepted: 25 June 1998 相似文献
147.
José C. Aponte Abraham J. Vaisberg Denis Castillo German Gonzalez Yannick Estevez Jorge Arevalo Miguel Quiliano Mirko Zimic Manuela Verástegui Edith Málaga Robert H. Gilman Juan M. Bustamante Rick L. Tarleton Yuehong Wang Scott G. Franzblau Guido F. Pauli Michel Sauvain Gerald B. Hammond 《Bioorganic & medicinal chemistry》2010,18(8):2880-2886
The synthesis of 2-(5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)hydrazone-derivatives (BTPs) and their in vitro evaluation against Trypanosoma cruzi trypomastigotes, Mycobacterium tuberculosis, Leishmania amazonensis axenic amastigotes, and six human cancer cell lines is described. The in vivo activity of the most active and least toxic compounds against T. cruzi and L. amazonensis was also studied. BTPs constitute a new family of drug leads with potential activity against infectious diseases. Due to their drug-like properties, this series of compounds can potentially serve as templates for future drug-optimization and drug-development efforts for use as therapeutic agents in developing countries. 相似文献
148.
Daniele Castagnolo Fabrizio Manetti Marco Radi Beatrice Bechi Mafalda Pagano Alessandro De Logu Rita Meleddu Manuela Saddi Maurizio Botta 《Bioorganic & medicinal chemistry》2009,17(15):5716-5721
Two series of novel rigid pyrazolone derivatives were synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis. Two of these compounds showed a high activity against MTB (MIC = 4 μg/mL). The newly synthesized pyrazolones were also computationally investigated to analyze if their properties fit the pharmacophoric model for antitubercular compounds previously built by us. The results are in agreement with those reported by us previously for a class of pyrazole analogues and confirm the fundamental role of the p-chlorophenyl moiety at C4 in the antimycobacterial activity. 相似文献
149.
Manuela Battaglia Laura Strauss Maria‐Grazia Roncarolo 《The journal of gene medicine》2009,11(2):180-181
This Letter to the Editor has a published Response, which can be viewed using the link below. Response to Comment 相似文献
150.
Clemens Pachschw?ll Pedro Escobar García Manuela Winkler Gerald M. Schneeweiss Peter Sch?nswetter 《PloS one》2015,10(3)
Range shifts (especially during the Pleistocene), polyploidisation and hybridization are major factors affecting high-mountain biodiversity. A good system to study their role in the European high mountains is the Doronicum clusii aggregate (Asteraceae), whose four taxa (D. clusii s.s., D. stiriacum, D. glaciale subsp. glaciale and D. glaciale subsp. calcareum) are differentiated geographically, ecologically (basiphilous versus silicicolous) and/or via their ploidy levels (diploid versus tetraploid). Here, we use DNA sequences (three plastid and one nuclear spacer) and AFLP fingerprinting data generated for 58 populations to infer phylogenetic relationships, origin of polyploids—whose ploidy level was confirmed by chromosomally calibrated DNA ploidy level estimates—and phylogeographic history. Taxonomic conclusions were informed, among others, by a Gaussian clustering method for species delimitation using dominant multilocus data. Based on molecular data we identified three lineages: (i) silicicolous diploid D. clusii s.s. in the Alps, (ii) silicicolous tetraploid D. stiriacum in the eastern Alps (outside the range of D. clusii s.s.) and the Carpathians and (iii) the basiphilous diploids D. glaciale subsp. glaciale (eastern Alps) and D. glaciale subsp. calcareum (northeastern Alps); each taxon was identified as distinct by the Gaussian clustering, but the separation of D. glaciale subsp. calcareum and D. glaciale subsp. glaciale was not stable, supporting their taxonomic treatment as subspecies. Carpathian and Alpine populations of D. stiriacum were genetically differentiated suggesting phases of vicariance, probably during the Pleistocene. The origin (autopolyploid versus allopolyploid) of D. stiriacum remained unclear. Doronicum glaciale subsp. calcareum was genetically and morphologically weakly separated from D. glaciale subsp. glaciale but exhibited significantly higher genetic diversity and rarity. This suggests that the more widespread D. glaciale subsp. glaciale originated from D. glaciale subsp. calcareum, which is restricted to a prominent Pleistocene refugium previously identified in other alpine plant species. 相似文献