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Mohammad T. Mazhab-Jafari Christopher B. Marshall Jason Ho Noboru Ishiyama Vuk Stambolic Mitsuhiko Ikura 《The Journal of biological chemistry》2014,289(18):12195-12201
Constitutively activated variants of small GTPases, which provide valuable functional probes of their role in cellular signaling pathways, can often be generated by mutating the canonical catalytic residue (e.g. Ras Q61L) to impair GTP hydrolysis. However, this general approach is ineffective for a substantial fraction of the small GTPase family in which this residue is not conserved (e.g. Rap) or not catalytic (e.g. Rheb). Using a novel engineering approach, we have manipulated nucleotide binding through structure-guided substitutions of an ultraconserved glycine residue in the G3-box motif (DXXG). Substitution of Rheb Gly-63 with alanine impaired both intrinsic and TSC2 GTPase-activating protein (GAP)-mediated GTP hydrolysis by displacing the hydrolytic water molecule, whereas introduction of a bulkier valine side chain selectively blocked GTP binding by steric occlusion of the γ-phosphate. Rheb G63A stimulated phosphorylation of the mTORC1 substrate p70S6 kinase more strongly than wild-type, thus offering a new tool for mammalian target of rapamycin (mTOR) signaling. 相似文献
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Libyan Thymus capitatus essential oil: antioxidant,antimicrobial, cytotoxic and colon pathogen adhesion‐inhibition properties 下载免费PDF全文
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Danijela Mišić Branislav Šiler Jasmina Nestorović Živković Ana Simonović Vuk Maksimović Snežana Budimir Dušica Janošević Milutin Đuričković Miroslav Nikolić 《Plant Cell, Tissue and Organ Culture》2012,108(3):389-400
The effect of reduced availability of sugars on growth and essential metabolic processes in roots, resulting from decreased
photosynthesis under salinity, was excluded by establishing a non-photosynthetic model-system in this study: root cultures
of Centaurium maritimum (L.) Fritch and Centaurium spicatum (L.) Fritch. The contribution of inorganic cations and organic compounds (e.g. carbohydrates and amino acids) to the osmotic
adjustment (OA) in roots during short-term exposure to various salt concentrations (0, 50, 100 or 200 mM NaCl) was emphasized.
Observed morphological and histological changes in roots were species specific, and were dependent on salinity level. Although
C. spicatum appears to be more tolerant to salt stress, both species employed similar strategies in response to elevated salinity to
different extents, and displayed effective OA mechanisms. Under low and moderate salinity, inorganic cations were the major
contributors to OA in roots of both species, followed by soluble sugars, while the relative contribution of proline (Pro)
and free amino acids was insignificant. Osmotic adjustment under severe stress appears to be mediated by increased accumulation
of organic compounds. The analysis of the intraspecies variability in salt response of C. spicatum and C. maritimum roots enabled the identification of some organic compounds which could be used as potential biochemical markers in screening
for salt tolerance, including Pro in C. spicatum, and trehalose and polyols in C. maritimum. 相似文献
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D Mišić M Dragićević B Siler J Nestorović Živković V Maksimović I Momčilović M Nikolic 《Journal of plant physiology》2012,169(13):1281-1289
A heterotrophic model system was established in our studies in order to differentiate the effect of high salt concentrations in external medium on growth and sugar metabolism in roots from the effect of reduced sugar availability resulting from decreased photosynthesis under salinity. Soluble sugar content and the activity of acid invertase in root cultures of salt-tolerant (ST) and salt-sensitive (SS) Schenkia spicata (L.) Mansion genotypes were investigated during exposure to different NaCl concentrations (0-200mM). Their response to severe salinity was characterized by a metabolic adjustment that led to the accumulation of sucrose (Suc) in root tissues. There was clear evidence that cell wall invertase (CW-Inv) is the major contributor to the Suc/hexose ratio in roots during exposure to elevated salinity. The results of CW-Inv activity and immunodetection assays in our study suggest that the regulation of CW-Inv expression is most likely achieved in a salt stress dependent manner. Also, NaCl modulated soluble acid invertase (SA-Inv) expression differentially in SS and ST genotypes of S. spicata. Regardless of the salt treatment, genotype, or the amount of enzyme, SA-Inv activity was generally low, indicating regulation at the posttranslational level. The results suggest no direct role of SA-Inv in the regulation of the root tissue carbohydrate pool and therefore in the control of the availability of glucose and fructose for the primary metabolism and/or osmotic adjustment in the present heterotrophic model system. 相似文献
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PTEN function in mammalian cell size regulation 总被引:21,自引:0,他引:21
The PTEN tumor suppressor gene is a lipid phosphatase that negatively regulates cell survival mediated by the phosphatidyl inositol 3' kinase-protein kinase B/Akt signaling pathway. Recent in vivo studies have revealed a novel role for PTEN in the size control of neurons. Dysregulation of cell growth control by PTEN is associated with the neurological disorder Lhermitte-Duclos disease. PTEN may regulate cell size through effects on protein translation. 相似文献
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We present a dynamic network model of corrupt and noncorrupt employees representing two states in the public and private sector. Corrupt employees are more connected to one another and are less willing to change their attitudes regarding corruption than noncorrupt employees. This behavior enables them to prevail and become the majority in the workforce through a first-order phase transition even though they initially represented a minority. In the model, democracy—understood as the principle of majority rule—does not create corruption, but it serves as a mechanism that preserves corruption in the long run. The motivation for our network model is a paradox that exists on the labor market. Although economic theory indicates that higher risk investments should lead to larger rewards, in many developed and developing countries workers in lower-risk public sector jobs are paid more than workers in higher-risk private sector jobs. To determine the long-run sustainability of this economic paradox, we study data from 28 EU countries and find that the public sector wage premium increases with the level of corruption. 相似文献
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Aleksandar Mikić Petr Smýkal Gregory Kenicer Margarita Vishnyakova Nune Sarukhanyan Janna A. Akopian Armen Vanyan Ivan Gabrielyan Iva Smýkalová Ekaterina Sherbakova Lana Zorić Jovanka Atlagić Tijana Zeremski-Škorić Branko Ćupina Đorđe Krstić Igor Jajić Svetlana Antanasović Vuk Đorđević Vojislav Mihailović Alexandr Ivanov Sergio Ochatt Cengiz Toker Bojan Zlatković Mike Ambrose 《Planta》2014,240(5):1147-1147
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Milan ?i?i? Miroslav ?ivi? Vuk Maksimovi? Marina Stani? Strahinja Kri?ak Tijana Cveti? Anti? Joanna Zakrzewska 《PloS one》2014,9(7)
The biological and chemical basis of vanadium action in fungi is relatively poorly understood. In the present study, we investigate the influence of vanadate (V5+) on phosphate metabolism of Phycomyces blakesleeanus. Addition of V5+ caused increase of sugar phosphates signal intensities in 31P NMR spectra in
vivo. HPLC analysis of mycelial phosphate extracts demonstrated increased concentrations of glucose 6 phosphate, fructose 6 phosphate, fructose 1, 6 phosphate and glucose 1 phosphate after V5+ treatment. Influence of V5+ on the levels of fructose 2, 6 phosphate, glucosamine 6 phosphate and glucose 1, 6 phosphate (HPLC), and polyphosphates, UDPG and ATP (31P NMR) was also established. Increase of sugar phosphates content was not observed after addition of vanadyl (V4+), indicating that only vanadate influences its metabolism. Obtained results from in
vivo experiments indicate catalytic/inhibitory vanadate action on enzymes involved in reactions of glycolysis and glycogenesis i.e., phosphoglucomutase, phosphofructokinase and glycogen phosphorylase in filamentous fungi. 相似文献