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61.
Proteome and phosphoproteome analysis of starch granule-associated proteins from normal maize and mutants affected in starch biosynthesis 总被引:2,自引:0,他引:2
Grimaud F Rogniaux H James MG Myers AM Planchot V 《Journal of experimental botany》2008,59(12):3395-3406
In addition to the exclusively granule-bound starch synthase GBSSI, starch granules also bind significant proportions of other starch biosynthetic enzymes, particularly starch synthases (SS) SSI and SSIIa, and starch branching enzyme (BE) BEIIb. Whether this association is a functional aspect of starch biosynthesis, or results from non-specific entrapment during amylopectin crystallization, is not known. This study utilized genetic, immunological, and proteomic approaches to investigate comprehensively the proteome and phosphoproteome of Zea mays endosperm starch granules. SSIII, BEI, BEIIa, and starch phosphorylase were identified as internal granule-associated proteins in maize endosperm, along with the previously identified proteins GBSS, SSI, SSIIa, and BEIIb. Genetic analyses revealed three instances in which granule association of one protein is affected by the absence of another biosynthetic enzyme. First, eliminating SSIIa caused reduced granule association of SSI and BEIIb, without affecting GBSS abundance. Second, eliminating SSIII caused the appearance of two distinct electrophoretic mobility forms of BEIIb, whereas only a single migration form of BEIIb was observed in wild type or any other mutant granules examined. Third, eliminating BEIIb caused significant increases in the abundance of BEI, BEIIa, SSIII, and starch phosphorylase in the granule, without affecting SSI or SSIIa. Analysis of the granule phosphoproteome with a phosphorylation-specific dye indicated that GBSS, BEIIb, and starch phosphorylase are all phosphorylated as they occur in the granule. These results suggest the possibility that starch metabolic enzymes located in granules are regulated by post-translational modification and/or protein-protein interactions. 相似文献
62.
Fos C Salles A Lang V Carrette F Audebert S Pastor S Ghiotto M Olive D Bismuth G Nunès JA 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(3):1969-1977
ICOS ligation in concert with TCR stimulation results in strong PI3K activation in T lymphocytes. The ICOS cytoplasmic tail contains an YMFM motif that binds the p85alpha subunit of class IA PI3K, similar to the YMNM motif of CD28, suggesting a redundant function of the two receptors in PI3K signaling. However, ICOS costimulation shows greater PI3K activity than CD28 in T cells. We show in this report that ICOS expression in activated T cells triggers the participation of p50alpha, one of the regulatory subunits of class IA PI3Ks. Using different T-APC cell conjugate systems, we report that p50alpha accumulates at the immunological synapse in activated but not in resting T cells. Our results demonstrate that ICOS membrane expression is involved in this process and that p50alpha plasma membrane accumulation requires a functional YMFM Src homology 2 domain-binding motif in ICOS. We also show that ICOS triggering with its ligand, ICOSL, induces the recruitment of p50alpha at the synapse of T cell/APC conjugates. In association with the p110 catalytic subunit, p50alpha is known to carry a stronger lipid kinase activity compared with p85alpha. Accordingly, we observed that ICOS engagement results in a stronger activation of PI3K. Together, these findings provide evidence that p50alpha is likely a determining factor in ICOS-mediated PI3K activity in T cells. These results also suggest that a differential recruitment and activity of class IA PI3K subunits represents a novel mechanism in the control of PI3K signaling by costimulatory molecules. 相似文献
63.
Prudent R Moucadel V López-Ramos M Aci S Laudet B Mouawad L Barette C Einhorn J Einhorn C Denis JN Bisson G Schmidt F Roy S Lafanechere L Florent JC Cochet C 《Molecular and cellular biochemistry》2008,316(1-2):71-85
None of the already described CK2 inhibitors did fulfill the requirements for successful clinical settings. In order to find innovative CK2 inhibitors based on new scaffolds, we have performed a high-throughput screening of diverse chemical libraries. We report here the identification and characterization of several classes of new inhibitors. Whereas some share characteristics of previously known CK2 inhibitors, others are chemically unrelated and may represent new opportunities for the development of better CK2 inhibitors. By combining structure-activity relationships with a docking procedure, we were able to determine the binding mode of these inhibitors. Interestingly, beside the identification of several nanomolar ATP-competitive inhibitors, one class of chemical inhibitors displays a non-ATP competitive mode of inhibition, a feature that suggests that CK2 possess distinct druggable binding sites. For the most promising inhibitors, selectivity profiling was performed. We also provide evidence that some chemical compounds are inhibiting CK2 in living cells. Finally, the collected data allowed us to draw the rules about the chemical requirements for CK2 inhibition both in vitro and in a cellular context. 相似文献
64.
Roger Miras Isabelle Morin Florent Guillain Elisabeth Mintz 《Journal of biological inorganic chemistry》2008,13(2):195-205
Copper is both an essential element as a catalytic cofactor and a toxic element because of its redox properties. Once in the
cell, Cu(I) binds to glutathione (GSH) and various thiol-rich proteins that sequester and/or exchange copper with other intracellular
components. Among them, the Cu(I) chaperone Atx1 is known to deliver Cu(I) to Ccc2, the Golgi Cu–ATPase, in yeast. However,
the mechanism for Cu(I) incorporation into Atx1 has not yet been unraveled. We investigated here a possible role of GSH in
Cu(I) binding to Atx1. Yeast Atx1 was expressed in Escherichia coli and purified to study its ability to bind Cu(I). We found that with an excess of GSH [at least two GSH/Cu(I)], Atx1 formed
a Cu(I)-bridged dimer of high affinity for Cu(I), containing two Cu(I) and two GSH, whereas no dimer was observed in the absence
of GSH. The stability constants (log β) of the Cu(I) complexes measured at pH 6 were 15–16 and 49–50 for CuAtx1 and Cu2I(GS−)2(Atx1)2, respectively. Hence, these results suggest that in vivo the high GSH concentration favors Atx1 dimerization and that Cu2I(GS−)2(Atx1)2 is the major conformation of Atx1 in the cytosol. 相似文献
65.
Pierrick Fevrier Philippe Gugan Florent Yvergnaux Jean Pierre Callegari Laurent Dufoss Adrien Binet 《Journal of Molecular Catalysis .B, Enzymatic》2001,11(4-6):445-453
Preliminary investigations on the regioselectiviy of various lipases were performed. Ten commercial lipases from different origins, including three immobilized lipases, were tested by esterification reaction between caprylic acid and propyl or isopropyl alcohol in n-hexane. Reaction products were analyzed with a gas chromatograph. Best yields were obtained with immobilized lipase IM60 from Rhizomucor miehei. Therefore, this enzyme was chosen as biocatalyst for a second step of regioselectiviy study with propylene glycol which bears primary and secondary alcohol groups. It was shown, by using several solvents, that polarity could influence the product profile in situations in which multiple products of various polarities can be formed. Furthermore, the major role of silica gel in reaction mixture was established. 相似文献
66.
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68.
Cancer cell dissemination away from the primary tumor and their ability to form metastases remain the major causes of death from cancer. Understanding the molecular mechanisms triggering this event could lead to the design of new cancer treatments. The establishment and the maintenance of tissue architecture depend on the coordination of cell behavior within this tissue. Cell-cell interactions must form adhesive structures between neighboring cells while remaining highly dynamic to allow and control tissue renewal or remodeling. Among intercellular junctions, cadherin-based adherens junctions mediate strong physical interactions and transmit information from the cell microenvironment to the cytoplasm. Disruption of these cell-cell contacts perturbs the polarity of epithelial tissues leading to their disorganization and ultimately to aggressive carcinomas. In non-epithelial tissues, the role of cadherins in the development of cancer is still debated. We recently found that downregulation of N-cadherin in malignant glioma—the most frequent primary brain tumor—results in cell polarization defects leading to abnormal motile behavior with increased cell speed and decreased persistence in directionality. Re-expression of N-cadherin in glioma cells restores cell polarity and limits glioma cell migration, providing a potential therapeutic tool for diffuse glioma. 相似文献
69.
Assia Ben Braiek Hinda Chahed Florent Dumont Fodha Abdelhak Denguir Hichem Habib Gamra Bruno Baudin 《Journal of cellular and molecular medicine》2021,25(3):1518-1530
Matrix metalloproteinases (MMPs) are implicated in atherosclerotic plaque rupture and recondition. Specific tissue inhibitors (TIMPs) control MMP functions. Both MMPs and TIMPs are potential biomarkers of plaque instability. Elevated Apo-CII and CIII and Apo-E levels are recognized as cardiovascular disease risk factors. We aimed to establish the best blood biomarker panel to evaluate the coronary artery disease (CAD) severity. Plasma levels of MMP-3 and MMP-9, TIMP-1 and TIMP-2, Apo-CII, Apo-CIII and Apo-E were measured in 472 patients with CAD evaluated by coronary angiography and electrocardiography, and in 285 healthy controls. MMP-3 and MMP-9 plasma levels in CAD patients were significantly increased (P < 0.001) compared to controls (3.54- and 3.81-fold, respectively). Furthermore, these increments are modulated by CAD severity as well as for Apo-CII and Apo-CIII levels (P < 0.001). TIMPs levels were decreased in CAD versus controls (P < 0.001) and in inverse correlation to MMPs. Standard ROC curve approach showed the importance of panels of biomarkers, including MMP-3, MMP-9, TIMP-1, TIMP-2, Apo-CII and Apo-CIII, for disease aggravation diagnosis. A high area under curve (AUC) value (0.995) was reached for the association of MMP-9, TIMP-2 and Apo-CIII. The unbalance between MMPs and TIMPs in vascular wall and dyslipidaemia creates favourable conditions for plaque disruption. Our study suggests that the combination of MMP-9, TIMP-2 and Apo-CIII values (‘CAD aggravation panel’) characterizes the severity of CAD, that is electrophysiological state, number of involved vessels, stent disposal and type of stent. 相似文献
70.