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21.
Bryja V Pacherník J Faldíková L Krejcí P Pogue R Nevrivá I Dvorák P Hampl A 《Biochimica et biophysica acta》2004,1691(2-3):105-116
This in vivo study employs p27-deficient mice to investigate the significance of p27 for the metabolism of D-type cyclins in differentiated cells. The absence of p27 results in decreased levels of cyclins D2 and/or D3 in some organs. As demonstrated on Leydig cells of testis, such dependency is only restricted to certain cell types including terminally differentiated ones, and the absence of p27 in these cells can interfere with their differentiation. The decrease of cyclin D caused by the absence of p27 equals the amount of cyclin D physically associated with p27 in non-mutant animals. The data indicate that it is the proportion of p27-associated cyclin D that determines the response to p27 deficiency. Cells in which the level of D-type cyclin is dependent on p27 do not up-regulate the activity of their CDK2 and CDK4 upon loss of p27, and these cells have a negligible amount of p27 bound to CDK2 and/or cyclin A/E under normal conditions. Together, the findings suggest the existence of a dual role for p27, one being a classical regulation of cell cycle via inhibition of cyclin-dependent kinases (CDK), and the other being participation in the establishment and/or maintenance of differentiated status that is realized in conjunction with D-type cyclins. 相似文献
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Stadthagen G Jackson M Charles P Boudou F Barilone N Huerre M Constant P Liav A Bottova I Nigou J Brando T Puzo G Daffé M Benjamin P Coade S Buxton RS Tascon RE Rae A Robertson BD Lowrie DB Young DB Gicquel B Griffin R 《Microbes and infection / Institut Pasteur》2006,8(8):2245-2253
p-Hydroxybenzoic acid derivatives (p-HBADs) are glycoconjugates secreted by all Mycobacterium tuberculosis isolates whose contribution to pathogenicity remains to be determined. The pathogenicity of three transposon mutants of M. tuberculosis deficient in the biosynthesis of some or all forms of p-HBADs was studied. Whilst the mutants grew similarly to the wild-type strain in macrophages and C57BL/6 mice, two of the mutants induced a more severe and diffuse inflammation in the lungs. The lack of production of some or all forms of p-HBADs in these two mutants also correlated with an increased secretion of the pro-inflammatory cytokines tumour-necrosis factor alpha, interleukin 6 and interleukin 12 in vivo. We propose that the loss of production of p-HBADs by tubercle bacilli results in their diminished ability to suppress the pro-inflammatory response to infection and that this ultimately provokes extensive pulmonary lesions in the C57BL/6 model of tuberculosis infection. 相似文献
23.
Andres Jaanus Susanna Hajdu Seppo Kaitala Agneta Andersson Kaire Kaljurand Iveta Ledaine Inga Lips Irina Olenina 《Hydrobiologia》2006,554(1):137-146
During the latest years medium-sized (15–30 μm), single-celled dinoflagellates have been reported to form blooms in the northern
Baltic Proper and the Gulf of Finland in winter and spring. Recent studies (Kremp et al., 2003. Proceedings of the 7th International conference of Modern and Fossil Dinoflagellates, September 21–25, Nagasaki, Japan,
66 pp.) indicate that those blooms are caused by two isomorphic species – Scrippsiella hangoei (Schiller) Larsen, and a new species, tentatively belonging to the genus Woloszynskia. Until now there has been no report on how widely distributed these phytoplankton species are in the Baltic Sea. In this
study, the occurrence of Scrippsiella/Woloszynskia complex in the entire Baltic Sea was investigated, by using monitoring data from 1997 to 2003. The species occurred in a
salinity range from 2 to 8 PSU. Highest concentrations were observed at salinity 4.5–6.5 PSU. Maximum cell densities of Scrippsiella/Woloszynskia complex in the water column were mainly obtained in April or in the beginning of May by the water temperature <3 °C prior
to stratification was formed. In the central Gulf of Finland, the second maximum was found in 1999 and 2002 by the temperature
>6 °C. Bloom formations in the Baltic Proper and in the Gulf of Finland may not only be explained by optimum temperature and
salinity, but also with other factors e.g. high nutrient concentrations and good seeding conditions from the sediments. 相似文献
24.
We have previously reported (Dobreva, I., Waeber, G., Mooser, V., James, R. W., and Widmann, C. (2003) J. Lipid Res. 44, 2382-2390) that low density lipoproteins (LDLs) induce activation of the p38 MAPK pathway, resulting in fibroblast spreading and lamellipodia formation. Here, we show that LDL-stimulated fibroblast spreading and wound sealing are due to secretion of a soluble factor. Using an antibody-based human protein array, interleukin-8 (IL-8) was identified as the main cytokine whose concentration was increased in supernatants from LDL-stimulated cells. Incubation of supernatants from LDL-treated cells with an anti-IL-8 blocking antibody completely abolished their ability to induce cell spreading and mediate wound closure. In addition, fibroblasts treated with recombinant IL-8 spread to the same extent as cells incubated with LDL or supernatants from LDL-treated cells. The ability of LDL and IL-8 to induce fibroblast spreading was mediated by the IL-8 receptor type II (CXCR-2). Furthermore, LDL-induced IL-8 production and subsequent wound closure required the activation of the p38 MAPK pathway, because both processes were abrogated by a specific p38 inhibitor. Therefore, the capacity of LDLs to induce fibroblast spreading and accelerate wound closure relies on their ability to stimulate IL-8 secretion in a p38 MAPK-dependent manner. Regulation of fibroblast shape and migration by lipoproteins may be relevant to atherosclerosis that is characterized by increased LDL cholesterol levels, IL-8 production, and extensive remodeling of the vessel wall. 相似文献
25.
Gresner P Dolník M Waczulíková I Bryszewska M Sikurová L Watala C 《Biochimica et biophysica acta》2006,1760(2):207-215
Hydrolysis of acetylsalicylic acid (ASA, aspirin), an antiplatelet drug commonly used in the prevention of stroke and myocardial infarction, seems to play a crucial role in its pharmacological action. Thirty-eight healthy volunteers and 38 type 2 diabetic patients were enrolled to test the hypothesis that the enhanced plasma degradation and lowered bioavailability of ASA in diabetic patients is associated with the attenuation of platelet response. Aspirin esterase activities were tested at pH 7.4 and 5.5. A significantly higher overall aspirin esterase activity was noted at pH 7.4 in the diabetic patients (P<0.003), corresponding to faster ASA hydrolysis (P<0.006). This increased activity was attributable to butyrylcholinesterase and probably to albumin, because it was effectively inhibited by eserine and 4-bis-nitrophenyl phosphate (P<0.01). No significant differences between control and diabetic subjects were found at pH 5.5 in either enzymatic activities or ASA hydrolysis rates. The enhanced plasma ASA degradation in diabetic subjects was significantly associated with the refractoriness of blood platelets to ASA (P<0.05) and modulated by plasma cholesterol (P<0.01). No direct effects of plasma pH or albumin were observed. In conclusion, higher aspirin esterase activity contributes to the lowered response of diabetic platelets to ASA-mediated antiplatelet therapy. 相似文献
26.
The structures of fully active cyclin-dependent kinase-2 (CDK2) complexed with ATP and peptide substrate, CDK2 after the catalytic
reaction, and CDK2 inhibited by phosphorylation at Thr14/Tyr15 were studied using molecular dynamics (MD) simulations. The
structural details of the CDK2 catalytic site and CDK2 substrate binding box were described. Comparison of MD simulations
of inhibited complexes of CDK2 was used to help understand the role of inhibitory phosphorylation at Thr14/Tyr15. Phosphorylation
at Thr14/Tyr15 causes ATP misalignment for the phosphate-group transfer, changes in the Mg2+ coordination sphere, and changes in the H-bond network formed by CDK2 catalytic residues (Asp127, Lys129, Asn132). The inhibitory
phosphorylation causes the G-loop to shift from the ATP binding site, which leads to opening of the CDK2 substrate binding
box, thus probably weakening substrate binding. All these effects explain the decrease in kinase activity observed after inhibitory
phosphorylation at Thr14/Tyr15 in the G-loop. Interaction of the peptide substrate, and the phosphorylated peptide product,
with CDK2 was also studied and compared. These results broaden hypotheses drawn from our previous MD studies as to why a basic
residue (Arg/Lys) is preferred at the P+2 substrate position.
Figure View of the substrate binding site of the fully active cyclin-dependent kinase-2 (CDK2) (pT160-CDK2/cyclin A/ATP). The pThr160 activation site is located in the T-loop (yellow secondary structure). The G-loop, which partly forms the ATP binding site, is shown in blue. The Thr14 and Tyr15 inhibitory phosphorylation sites located in the G-loop are shown in licorice representation 相似文献
27.
Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization
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Fielding AB Dobreva I McDonald PC Foster LJ Dedhar S 《The Journal of cell biology》2008,180(4):681-689
Integrin-linked kinase (ILK) is a serine-threonine kinase and scaffold protein with well defined roles in focal adhesions in integrin-mediated cell adhesion, spreading, migration, and signaling. Using mass spectrometry-based proteomic approaches, we identify centrosomal and mitotic spindle proteins as interactors of ILK. alpha- and beta-tubulin, ch-TOG (XMAP215), and RUVBL1 associate with ILK and colocalize with it to mitotic centrosomes. Inhibition of ILK activity or expression induces profound apoptosis-independent defects in the organization of the mitotic spindle and DNA segregation. ILK fails to localize to the centrosomes of abnormal spindles in RUVBL1-depleted cells. Additionally, depletion of ILK expression or inhibition of its activity inhibits Aurora A-TACC3/ch-TOG interactions, which are essential for spindle pole organization and mitosis. These data demonstrate a critical and unexpected function for ILK in the organization of centrosomal protein complexes during mitotic spindle assembly and DNA segregation. 相似文献
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