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131.
132.
Filipp D Moemeni B Ferzoco A Kathirkamathamby K Zhang J Ballek O Davidson D Veillette A Julius M 《The Journal of biological chemistry》2008,283(39):26409-26422
Mechanisms regulating the activation and delivery of function of Lck and Fyn are central to the generation of the most proximal signaling events emanating from the T cell antigen receptor (TcR) complex. Recent results demonstrate that lipid rafts (LR) segregate Lck and Fyn and play a fundamental role in the temporal and spatial coordination of their activation. Specifically, TcR-CD4 co-aggregation-induced Lck activation outside LR results in Lck translocation to LR where the activation of LR-resident Fyn ensues. Here we report a structure-function analysis toward characterizing the mechanism supporting Lck partitioning to LR and its capacity to activate co-localized Fyn. Using NIH 3T3 cells ectopically expressing FynT, we demonstrate that only LR-associated, kinase-active (Y505F)Lck reciprocally co-immunoprecipitates with and activates Fyn. Mutational analyses revealed a profound reduction in the formation of Lck-Fyn complexes and Fyn activation, using kinase domain mutants K273R and Y394F of (Y505F)Lck, both of which have profoundly compromised kinase activity. The only kinase-active Lck mutants tested that revealed impaired physical and enzymatic engagement with Fyn were those involving truncation of the C-terminal sequence YQPQP. Remarkably, sequential truncation of YQPQP resulted in an increasing reduction of kinase-active Lck partitioning to LR, in both fibroblasts and T cells. This in turn correlated with an ablation of the capacity of these truncates to enhance TcR-mediated interleukin-2 production. Thus, Lck-dependent Fyn activation is predicated by proximity-mediated transphosphorylation of the Fyn kinase domain, and targeting kinase-active Lck to LR is dependent on the C-terminal sequence QPQP. 相似文献
133.
Mathara JM Schillinger U Kutima PM Mbugua SK Guigas C Franz C Holzapfel WH 《Current microbiology》2008,56(4):315-321
Lactobacillus plantarum was the major species among the lactic acid bacterial strains isolated from traditional fermented milk of the Maasai in Kenya.
Selected strains were characterized for their functional properties using in vitro standard procedures. All strains expressed
acid tolerance at pH 2.0 after 2-h exposure of values that ranged from 1% to 100%, while bile tolerance of acid-stressed cells
at 0.3% oxgal varied from 30% to 80%. In vitro adhesion to the mucus-secreting cell line HT 29 MTX and binding capacity to
extracellular protein matrices was demonstrated for several strains. The four strains tested in a simulated stomach duodenum
passage survived with recovery rates ranging from 17% to 100%. Strains were intrinsically resistant to several antibiotics
tested. From these in vitro studies, a number of Lb. plantarum strains isolated from the Maasai traditional fermented milk showed probiotic potential. The strains are good candidates for
multifunctional starter culture development. 相似文献
134.
A homogeneous cellular histone deacetylase assay suitable for compound profiling and robotic screening 总被引:1,自引:1,他引:0
Most cellular assays that quantify the efficacy of histone deacetylase (HDAC) inhibitors measure hyperacetylation of core histone proteins H3 and H4. Here we describe a new approach, directly measuring cellular HDAC enzymatic activity using the substrate Boc-K(Ac)-7-amino-4-methylcoumarin (AMC). After penetration into HeLa cervical carcinoma or K562 chronic myeloid leukemia cells, the deacetylated product Boc-K-AMC is formed which, after cell lysis, is cleaved by trypsin, finally releasing the fluorophor AMC. The cellular potency of suberoylanilide hydroxamic acid, LBH589, trichostatin A, and MS275 as well-known HDAC inhibitors was determined using this assay. IC(50) values derived from concentration-effect curves correlated well with EC(50) values derived from a cellomics array scan histone H3 hyperacetylation assay. The cellular HDAC activity assay was adapted to a homogeneous format, fully compatible with robotic screening. Concentration-effect curves generated on a Tecan Genesis Freedom workstation were highly reproducible with a signal-to-noise ratio of 5.7 and a Z' factor of 0.88, indicating a very robust assay. Finally, a HDAC-inhibitor focused library was profiled in a medium-throughput screening campaign. Inhibition of cellular HDAC activity correlated well with cytotoxicity and histone H3 hyperacetylation in HeLa cells and with inhibition of human recombinant HDAC1 in a biochemical assay. Thus, by using Boc-K(Ac)-AMC as a cell-permeable HDAC substrate, the activity of various protein lysine-specific deacetylases including HDAC1-containing complexes is measurable in intact cells in a simple and homogeneous manner. 相似文献
135.
Guibin Ma Andrey Ilyukhin Julius Glaser Imre Tth Lszl Zkny 《Inorganica chimica acta》2001,320(1-2):92-100
The formation of three [Tl(en)n]3+ complexes (n=1–3) in a pyridine solvent has been established by means of 205Tl and 1H NMR. Their stepwise stability constants based on concentrations, Kn=[Tl(en)n 3+]/{[Tl(en)n−1 3+]·[en]}, at 298 K in 0.5 M NaClO4 ionic medium in pyridine, were calculated from 205Tl NMR integrals: log K1=7.6±0.7; log K2=5.2±0.5 and log K3=2.64±0.05. Linear correlation between both the 205Tl NMR shifts and spin–spin coupling 205Tl–1H versus the stability constants has been found and discussed. A single crystal with the composition [Tl(en)3](ClO4)3 was synthesized and its structure determined by X-ray diffraction. The Tl3+ ion is coordinated by three ethylenediamine ligands via six N-donor atoms in a distorted octahedral fashion. 相似文献
136.
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139.
Julius Schwemmle 《Molecular & general genetics : MGG》1924,34(1):145-185
Ohne Zusammenfassung 相似文献
140.
U Julius W Leonhardt H Schneider K Schollberg M Hanefeld J Schulze H Haller 《Endokrinologie》1979,73(2):214-220
In 17 non-selected, non-hyperlipoproteinemic subjects without overt diabetes both adipose tissue biopsy and an oral glucose tolerance test (50 g) were performed. All persons were weight-stable at the time of investigation. A significant correlation between fasting insulin concentration and mean adipocyte volume was observed, whereas no correlation existed between ideal body weight index and fasting insulin level. Persons with larger adipocytes had elevated basal insulin levels as well as higher and longer lasting increments following the glucose challenge. They also exhibited significantly higher mean glucose levels during the OGTT. When these patients were matched for glucose tolerance with the subgroup having smaller mean adipocyte volumes, the difference in insulin levels was still demonstrable. This study underlines the importance of adipose-cell enlargement regulating basal and stimulated insulin output. 相似文献