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111.
de Nadal E Fadden RP Ruiz A Haystead T Ariño J 《The Journal of biological chemistry》2001,276(18):14829-14834
In vivo 32P-labeled yeast proteins from wild type and ppz1 ppz2 phosphatase mutants were resolved by bidimensional electrophoresis. A prominent phosphoprotein, which in ppz mutants showed a marked shift to acidic regions, was identified by mixed peptide sequencing as the translation elongation factor 1Balpha (formerly eEF1beta). An equivalent shift was detected in cells overexpressing HAL3, a inhibitory regulatory subunit of Ppz1. Subsequent analysis identified the conserved Ser-86 as the in vivo phosphorylatable residue and showed that its phosphorylation was increased in ppz cells. Pull-down experiments using a glutathione S-transferase (GST)-EF1Balpha fusion version allowed to identify Ppz1 as an in vivo interacting protein. Cells lacking Ppz display a higher tolerance to known translation inhibitors, such as hygromycin and paromomycin, and enhanced readthrough at all three nonsense codons, suggesting that translational fidelity might be affected. Overexpression of a GST-EF1Balpha fusion counteracted the growth defect associated to high levels of Ppz1 and this effect was essentially lost when the phosphorylatable Ser-86 is replaced by Ala. Therefore, the Ppz phosphatases appear to regulate the phosphorylation state of EF1Balpha in yeast, and this may result in modification of the translational accuracy. 相似文献
112.
Johan?PahlbergEmail author Magnus?Lindstr?m Petri?Ala-Laurila Nanna?Fyhrquist-Vanni Ari?Koskelainen Kristian?Donner 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2005,191(9):837-844
We report the first study of the relation between the wavelength of maximum absorbance (λmax) and the photoactivation energy (E
a) in invertebrate visual pigments. Two populations of the opossum shrimp Mysis relicta were compared. The two have been separated for 9,000 years and have adapted to different spectral environments (“Sea” and
“Lake”) with porphyropsins peaking at λmax=529 nm and 554 nm, respectively. The estimation of E
a was based on measurement of temperature effects on the spectral sensitivity of the eye. In accordance with theory (Stiles
in Transactions of the optical convention of the worshipful company of spectacle makers. Spectacle Makers’ Co., London, 1948), relative sensitivity to long wavelengths increased with rising temperature. The estimates calculated from this effect are
E
a,529=47.8±1.8 kcal/mol and E
a,554=41.5±0.7 kcal/mol (different at P<0.01). Thus the red-shift of λmax in the “Lake” population, correlating with the long-wavelength dominated light environment, is achieved by changes in the
opsin that decrease the energy gap between the ground state and the first excited state of the chromophore. We propose that
this will carry a cost in terms of increased thermal noise, and that evolutionary adaptation of the visual pigment to the
light environment is directed towards maximizing the signal-to-noise ratio rather than the quantum catch. 相似文献
113.
Induction of heat shock proteins in differentiated human and rodent neurons by celastrol 总被引:1,自引:0,他引:1 下载免费PDF全文
Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been termed protein misfolding disorders that are characterized by the neuronal accumulation of protein aggregates. Manipulation of the cellular stress-response involving induction of heat shock proteins (Hsps) in differentiated neurons offers a therapeutic strategy to counter conformational changes in neuronal proteins that trigger pathogenic cascades resulting in neurodegenerative diseases. Hsps are protein repair agents that provide a line of defense against misfolded, aggregation-prone proteins. These proteins are not induced in differentiated neurons by conventional heat shock. We have found that celastrol, a quinine methide triterpene, induced expression of a wider set of Hsps, including Hsp70B', in differentiated human neurons grown in tissue culture compared to cultured rodent neuronal cells. Hence the beneficial effect of celastrol against human neurodegenerative diseases may exceed its potential in rodent models of these diseases. 相似文献
114.
Frommer F Heinen TJ Wunderlich FT Yogev N Buch T Roers A Bettelli E Müller W Anderton SM Waisman A 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(8):5748-5759
B cells have been shown in various animal models to induce immunological tolerance leading to reduced immune responses and protection from autoimmunity. We show that interaction of B cells with naive T cells results in T cell triggering accompanied by the expression of negative costimulatory molecules such as PD-1, CTLA-4, B and T lymphocyte attenuator, and CD5. Following interaction with B cells, T cells were not induced to proliferate, in a process that was dependent on their expression of PD-1 and CTLA-4, but not CD5. In contrast, the T cells became sensitive to Ag-induced cell death. Our results demonstrate that B cells participate in the homeostasis of the immune system by ablation of conventional self-reactive T cells. 相似文献
115.
Morishige M Hashimoto S Ogawa E Toda Y Kotani H Hirose M Wei S Hashimoto A Yamada A Yano H Mazaki Y Kodama H Nio Y Manabe T Wada H Kobayashi H Sabe H 《Nature cell biology》2008,10(1):85-92
Epidermal growth factor (EGF) receptor (EGFR) signalling is implicated in tumour invasion and metastasis. However, whether there are EGFR signalling pathways specifically used for tumour invasion still remains elusive. Overexpression of Arf6 and its effector, AMAP1, correlates with and is crucial for the invasive phenotypes of different breast cancer cells. Here we identify the mechanism by which Arf6 is activated to induce tumour invasion. We found that GEP100/BRAG2, a guanine nucleotide exchanging factor (GEF) for Arf6, is responsible for the invasive activity of MDA-MB-231 breast cancer cells, whereas the other ArfGEFs are not. GEP100, through its pleckstrin homology domain, bound directly to Tyr1068/1086-phosphorylated EGFR to activate Arf6. Overexpression of GEP100, together with Arf6, caused non-invasive MCF7 cells to become invasive, which was dependent on EGF stimulation. Moreover, GEP100 knockdown blocked tumour metastasis. GEP100 was expressed in 70% of primary breast ductal carcinomas, and was preferentially co-expressed with EGFR in the malignant cases. Our results indicate that GEP100 links EGFR signalling to Arf6 activation to induce invasive activities of some breast cancer cells, and hence may contribute to their metastasis and malignancy. 相似文献
116.
Interactions between Newly Synthesized Glycoproteins, Calnexin and a Network of Resident Chaperones in the Endoplasmic Reticulum 总被引:8,自引:1,他引:8 下载免费PDF全文
Calnexin is a membrane-bound lectin and a molecular chaperone that binds newly synthesized glycoproteins in the endoplasmic reticulum (ER). To analyze the oligomeric properties of calnexin and calnexin-substrate complexes, sucrose velocity gradient centrifugation and chemical cross-linking were used. After CHAPS solubilization of Chinese Hamster Ovary cells, the unoccupied calnexin behaved as a monomer sedimenting at 3.5 S20,W. For calnexin-substrate complexes the S-values ranged between 3.5–8 S20,W, the size increasing with the molecular weight of the substrate. Influenza hemagglutinin, a well-characterized substrate associated with calnexin in complexes that sedimented at 5–5.5 S20,W. The majority of stable complexes extracted from cells, appeared to contain a single calnexin and a single substrate molecule, with about one third of the calnexin in the cell being unoccupied or present in weak associations. However, when chemical cross-linking was performed in intact cells, the calnexin-substrate complexes and calnexin itself was found to be part of a much larger heterogeneous protein network that included other ER proteins. Pulse-chase analysis of influenza-infected cells combined with chemical cross-linking showed that HA was part of large, heterogeneous, cross-linked entities during the early phases of folding, but no longer after homotrimer assembly. The network of weakly associated resident ER chaperones which included BiP, GRP94, calreticulin, calnexin, and other proteins, may serve as a matrix that binds early folding and assembly intermediates and restricts their exit from the ER. 相似文献
117.
Alon Abraham Majed Alabdali Abdulla Alsulaiman Ari Breiner Carolina Barnett Hans D. Katzberg Leif E. Lovblom Bruce A. Perkins Vera Bril 《PloS one》2016,11(11)
IntroductionSmall fiber neuropathy might be a part of typical mixed small and large fiber neuropathy, or a distinct entity, affecting exclusively small nerve fibers.ObjectivesExplore the utility of small nerve fiber testing in patients with clinical presentation suggesting small fiber neuropathy, with and without evidence for concomitant large fiber neuropathy.MethodsPatients attending the neuromuscular clinic from 2012 to 2015 with a clinical presentation suggesting small nerve fiber impairment, who had Laser Doppler flare imaging (LDIFlare) and quantitative thermal testing (QTT) were evaluated for this study. Patients with clinical or electrophysiological evidence for concomitant large fiber neuropathy were not excluded.ResultsThe sensitivities of LDIFlare, cooling and heat threshold testing were 64%, 36%, and 0% respectively for clinically highly suggestive small fiber neuropathy, 64%, 56%, and 19% respectively for mixed fiber neuropathy, and 86%, 79%, and 29% respectively for diabetic mixed fiber neuropathy.DiscussionLDIFlare and cooling thresholds testing are non-invasive small nerve fiber testing modalities, with moderate performance in patients with small and mixed fiber neuropathy, and excellent performance in diabetic mixed fiber neuropathy. 相似文献
118.
Type 2C Ser/Thr phosphatases are a remarkable class of protein phosphatases, which are conserved in eukaryotes and involved in a large variety of functional processes. Unlike in other Ser/Thr phosphatases, the catalytic polypeptide is not usually associated with regulatory subunits, and functional specificity is achieved by encoding multiple isoforms. For fungi, most information comes from the study of type 2C protein phosphatase (PP2C) enzymes in Saccharomyces cerevisiae, where seven PP2C-encoding genes (PTC1 to -7) with diverse functions can be found. More recently, data on several Candida albicans PP2C proteins became available, suggesting that some of them can be involved in virulence. In this work we review the available literature on fungal PP2Cs and explore sequence databases to provide a comprehensive overview of these enzymes in fungi. 相似文献
119.
Johan Watz Olle Calles Niclas Carlsson Teemu Collin Ari Huusko Jrgen Johnsson Per Anders Nilsson Johnny Norrgrd Daniel Nyqvist 《Freshwater Biology》2019,64(1):71-80
- Habitat structural complexity affects the behaviour and physiology of individuals, and responses to the environment can be immediate or influence performance later in life through delayed effects.
- Here, we investigated how structural enrichment, both pre‐release in the hatchery rearing environment and post‐release in the wild, influenced winter growth and site fidelity of brown trout stocked into side channels of a regulated river.
- Experiencing structural enrichment in the rearing environment during 3 months in autumn had no pre‐release effect on growth, but a delayed positive effect after release during the subsequent winter. Moreover, trout recaptured in wood‐treated sections of the side channels had grown more than trout recaptured in control sections. Wood enrichment in the side channels also increased overwinter site fidelity.
- These results show that adding structure during a relatively short period may alter growth trajectories, and adding wood to side channels is a cost‐effective method to enhance winter habitat carrying capacity for juvenile salmonids in regulated rivers.
120.
Individual protein tyrosine kinases and phosphatases target multiple substrates; this may generate conflicting signals, possibly within a single pathway. Protein-tyrosine phosphatase epsilon (PTPepsilon) performs two potentially opposing roles: in Neu-induced mammary tumors, PTPepsilon activates Src downstream of Neu, whereas in other systems PTPepsilon can indirectly down-regulate MAP kinase signaling. We now show that the latter effect is mediated at least in part via the adaptor protein Shc. PTPepsilon binds and dephosphorylates Shc in vivo, reducing the association of Shc with Grb2 and inhibiting downstream ERK activation. PTPepsilon binds Shc in a phosphotyrosine-independent manner mediated by the Shc PTB domain and aided by a sequence of 10 N-terminal residues in PTPepsilon. Surprisingly, PTPepsilon dephosphorylates Shc in a kinase-dependent manner; PTPepsilon targets Shc in the presence of Src but not in the presence of Neu. Using a series of point mutants of Shc and Neu, we show that Neu protects Shc from dephosphorylation by binding the PTB domain of Shc, most likely competing against PTPepsilon for binding the same domain. In agreement, PTPepsilon dephosphorylates Shc in mouse embryo fibroblasts but not in Neu-induced mammary tumor cells. We conclude that in the context of Neu-induced mammary tumor cells, Neu prevents PTPepsilon from targeting Shc and from reducing its promitogenic signal while phosphorylating PTPepsilon and directing it to activate Src in support of mitogenesis. In so doing, Neu contributes to the coherence of the promitogenic role of PTPepsilon in this system. 相似文献