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871.
Christopher J. Burns Michael F. Harte Xianyong Bu Emmanuelle Fantino Marilena Giarrusso Max Joffe Margarita Kurek Fiona S. Legge Pasquale Razzino Stephen Su Herbert Treutlein Soo San Wan Jun Zeng Andrew F. Wilks 《Bioorganic & medicinal chemistry letters》2009,19(4):1206-1209
A series of 2-(α-methylbenzylamino) pyrazines have shown to be potent inhibitors of the FMS tyrosine receptor kinase. Details of SAR studies, modeling and synthesis of compounds within this series are reported. 相似文献
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Joachim Garbrecht Triin Laos Elisabeth Holzer Margarita Dillinger Alexander Dammermann 《Current biology : CB》2021,31(11):2418-2428.e8
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M. Kellermayer Margarita Talas Connie Wong H. Busch Janet S. Butel 《Experimental cell research》1976,99(2):456-460
The solubility characteristics of SV40 tumor (T) antigen were investigated. Cell nuclei were isolated from cover glass cultures of SV 40-infected or transformed cells by detergent treatment. When treated in a buffered isotonic sucrose solution, the isolated nuclei contained typical SV40 T antigen by immunofluorescence. If the detergent was dissolved in an isotonic electrolyte solution containing 0.15 M monovalent cations (K+), the T antigen was extracted from the nuclei. Complement fixation tests demonstrated that the various solutions had no deleterious effects on the antigenicity of T antigen. Under identical conditions, the SV 40 capsid (V) antigen was not extracted from infected cell nuclei. These solubility characteristics place SV40 T antigen in the class of “loosely bound” nuclear proteins which includes non-histone proteins that appear to have cell regulatory functions. This supports the suggestion that the biological function of T antigen may be regulatory in nature. 相似文献
877.
Andreev YA Kozlov SA Koshelev SG Ivanova EA Monastyrnaya MM Kozlovskaya EP Grishin EV 《The Journal of biological chemistry》2008,283(35):23914-23921
Venomous animals from distinct phyla such as spiders, scorpions, snakes, cone snails, or sea anemones produce small toxic proteins interacting with a variety of cell targets. Their bites often cause pain. One of the ways of pain generation is the activation of TRPV1 channels. Screening of 30 different venoms from spiders and sea anemones for modulation of TRPV1 activity revealed inhibitors in tropical sea anemone Heteractis crispa venom. Several separation steps resulted in isolation of an inhibiting compound. This is a 56-residue-long polypeptide named APHC1 that has a Bos taurus trypsin inhibitor (BPTI)/Kunitz-type fold, mostly represented by serine protease inhibitors and ion channel blockers. APHC1 acted as a partial antagonist of capsaicin-induced currents (32 +/- 9% inhibition) with half-maximal effective concentration (EC(50)) 54 +/- 4 nm. In vivo, a 0.1 mg/kg dose of APHC1 significantly prolonged tail-flick latency and reduced capsaicin-induced acute pain. Therefore, our results can make an important contribution to the research into molecular mechanisms of TRPV1 modulation and help to solve the problem of overactivity of this receptor during a number of pathological processes in the organism. 相似文献
878.
At yeast vacuoles, phosphorylation of the HOPS subunit Vps41 depends on the Yck3 kinase. In a screen for mutants that mimic the yck3Delta phenotype, in which Vps41 accumulates in vacuolar dots, we observed that mutants in the V0-part of the V0/V1-ATPase, in particular in vma16Delta, also accumulate Vps41. This accumulation is not due to a phosphorylation defect, but to reduced release of Vps41 from vma16Delta vacuoles. One reason could be a connection to vacuole fission, which is blocked in V-ATPase mutants. Vacuole fusion is not impaired between vacuoles lacking the V0-subunits Vma16 or Vma6 and wild-type vacuoles, whereas fusion between mutant vacuoles is reduced. Our data suggest a connection between vacuole biogenesis and membrane fusion. 相似文献
879.
Regulation of glia number in Drosophila by Rap/Fzr, an activator of the anaphase-promoting complex, and Loco, an RGS protein 总被引:1,自引:0,他引:1
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Glia mediate a vast array of cellular processes and are critical for nervous system development and function. Despite their immense importance in neurobiology, glia remain understudied and the molecular mechanisms that direct their differentiation are poorly understood. Rap/Fzr is the Drosophila homolog of the mammalian Cdh1, a regulatory subunit of the anaphase-promoting complex/cyclosome (APC/C). APC/C is an E3 ubiquitin ligase complex well characterized for its role in cell cycle progression. In this study, we have uncovered a novel cellular role for Rap/Fzr. Loss of rap/fzr function leads to a marked increase in the number of glia in the nervous system of third instar larvae. Conversely, ectopic expression of UAS-rap/fzr, driven by repo-GAL4, results in the drastic reduction of glia. Data from clonal analyses using the MARCM technique show that Rap/Fzr regulates the differentiation of surface glia in the developing larval nervous system. Our genetic and biochemical data further indicate that Rap/Fzr regulates glial differentiation through its interaction with Loco, a regulator of G-protein signaling (RGS) protein and a known effector of glia specification. We propose that Rap/Fzr targets Loco for ubiquitination, thereby regulating glial differentiation in the developing nervous system. 相似文献
880.
Studies on the effect of eutrophication on the ecology of shallow lakes, usually pay scant attention to changes within the
epiphytic algal community, though the contribution of this to the ecosystem dynamics is transcendental. In order to test the
influence of nutrient loadings and fish densities in the structure of algal epiphyton in a shallow lake, an experiment was
performed using in situ mesocosms. Nutrient additions were related to significant decreases in the total epiphyton biovolume
and that of bacillariophyceans and zygnematophyceans, but with increases in the abundance of cyanobacteria. The different
response of algal groups at the higher nutrient concentrations (increases or decreases in their abundance and/or biovolume)
can be related to their ecophysiological constraints such as different resistance to toxicant ammonium accumulation. Plant-associated
macroinvertebrates numbers were positively correlated with total numbers of epiphyton. The presence of planktivorous fish
enhanced the abundance and biovolume of all algal groups, except cyanobacteria. Fishes enhanced the abundance of plant-associated
animals and of total epiphyton. Fish indirect effects (e.g., nutrients release) and their dietary particularities were among
the factors that together with nutrients influenced epiphyton growth. The role of indirect effects of fishes and the importance
of their dietary particularities are stressed as key factors to understand the processes controlling epiphyton ecology and
the food web structure of shallow lakes.
Handling editor: D. Ryder. 相似文献