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排序方式: 共有245条查询结果,搜索用时 31 毫秒
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Jiang S Seng S Avraham HK Fu Y Avraham S 《The Journal of biological chemistry》2007,282(16):12319-12329
Oligodendrocytes (OLGs) are generated by progenitor cells that are committed to differentiating into myelin-forming cells of the central nervous system. Rearrangement of the cytoskeleton leading to the extension of cellular processes is essential for the myelination of axons by OLGs. Here, we have characterized a new member of the Kelch-related protein family termed MRP2 (for Mayven-related protein 2) that is specifically expressed in brain. MRP2/KLHL1 is expressed in oligodendrocyte precursors and mature OLGs, and its expression is up-regulated during OLG differentiation. MRP2/KLHL1 expression was abundant during the specific stages of oligodendrocyte development, as identified by A2B5-, O4-, and O1-specific oligodendrocyte markers. MRP2/KLHL1 was localized in the cytoplasm and along the cell processes. Moreover, a direct endogenous association of MRP2/KLHL1 with actin was observed, which was significantly increased in differentiated OLGs compared with undifferentiated OLGs. Overexpression of MRP2/KLHL1 resulted in a significant increase in the process extension of rat OLGs, whereas MRP2/KLHL1 antisense reduced the process length of primary rat OLGs. Furthermore, murine OLGs isolated from MRP2/KLHL1 transgenic mice showed a significant increase in the process extension of OLGs compared with control wild-type murine OLGs. These studies provide insights into the role of MRP2/KLHL1, through its interaction with actin, in the process elongation of OLGs. 相似文献
23.
Noy A 《Current opinion in chemical biology》2011,15(5):710-718
Single molecule force spectroscopy presents a deceptively simple approach to probing interaction between molecules and molecular assemblies on the nanoscale by measuring forces that it takes to pull the molecules apart. Yet, a more detailed analysis reveals a wealth of different behaviors and interesting physics. This article aims to explore basic physical concepts behind these experiments from a strictly practical point of using these data to extract meaningful information about the interactions. It also focuses on different loading regimes in these experiments, different kinetics that they cause, and different data interpretation that is required for measurements in those regimes. 相似文献
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RAFTK/Pyk2 activation is mediated by trans-acting autophosphorylation in a Src-independent manner 总被引:1,自引:0,他引:1
The related adhesion focal tyrosine kinase (RAFTK), also known as Pyk2, undergoes autophosphorylation upon its stimulation. This leads to cascades of intracellular signaling that result in the regulation of various cellular activities. However, the molecular mechanism of RAFTK autophosphorylation is not yet known. Using various RAFTK constructs fused with two different tags, we found that the autophosphorylation of RAFTK was mediated by a trans-acting mechanism, not a cis-acting mechanism. In addition, overexpression of kinase-mutated RAFTK inhibited wild type RAFTK autophosphorylation in a dose-dependent manner by a trans-acting interaction. Trans-acting autophosphorylation was also observed between endogenous and exogenous RAFTK upon potassium depolarization of neuroendocrine PC12 cells. Using immunoprecipitation and affinity chromatography, we detected RAFTK self-association that was not affected by deletion of a single region or domain of RAFTK. Furthermore, RAFTK autophosphorylation occurred only at site Tyr402 in a Src kinase activity-independent manner. However, Src significantly enhanced RAFTK-mediated paxillin phosphorylation, suggesting a key role for Src in RAFTK activation and phosphorylation of downstream substrates. Our results indicate that the activation of RAFTK occurs in several steps. First, upon stimulus, RAFTK trans-autophosphorylates Tyr402. Second, phosphorylated Tyr402 recruits and activates Src kinase that in turn phosphorylates RAFTK and enhances its kinase activity. Lastly, the enhanced RAFTK activity induces the activation of downstream signaling molecules. Taken together, these studies provide insights into the molecular mechanism of RAFTK autophosphorylation and the specific role of Src in the regulation of RAFTK activation. 相似文献
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State of the art molecular dynamics simulations are used to study the structure, dynamics, molecular interaction properties and flexibility of DNA and RNA duplexes in aqueous solution. Special attention is paid to the deformability of both types of structures, revisiting concepts on the relative flexibility of DNA and RNA duplexes. Our simulations strongly suggest that the concepts of flexibility, rigidity and deformability are much more complex than usually believed, and that it is not always true that DNA is more flexible than RNA. 相似文献
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Shuxian Jiang Radoslaw Zagozdzon Meritxell Alberich Jorda Kalindi Parmar Yigong Fu John S. Williams Jodi Anne T. Wood Alexandros Makriyannis Naheed Banu Shalom Avraham Jerome E. Groopman Hava Karsenty Avraham 《The Journal of biological chemistry》2010,285(46):35471-35478
Endocannabinoids are lipid signaling molecules that act via G-coupled receptors, CB1 and CB2. The endocannabinoid system is capable of activation of distinct signaling pathways on demand in response to pathogenic events or stimuli, hereby enhancing cell survival and promoting tissue repair. However, the role of endocannabinoids in hematopoietic stem and progenitor cells (HSPCs) and their interaction with hematopoietic stem cells (HSC) niches is not known. HSPCs are maintained in the quiescent state in bone marrow (BM) niches by intrinsic and extrinsic signaling. We report that HSPCs express the CB1 receptors and that BM stromal cells secrete endocannabinoids, anandamide (AEA) (35 pg/107 cells), and 2-AG (75.2 ng/107 cells). In response to the endotoxin lipopolysaccharide (LPS), elevated levels of AEA (75.6 pg/107 cells) and 2-AG (98.8 ng/107 cells) were secreted from BM stromal cells, resulting in migration and trafficking of HSPCs from the BM niches to the peripheral blood. Furthermore, administration of exogenous cannabinoid CB1 agonists in vivo induced chemotaxis, migration, and mobilization of human and murine HSPCs. Cannabinoid receptor knock-out mice Cnr1−/− showed a decrease in side population (SP) cells, whereas fatty acid amide hydrolase (FAAH)−/− mice, which have elevated levels of AEA, yielded increased colony formation as compared with WT mice. In addition, G-CSF-induced mobilization in vivo was modulated by endocannabinoids and was inhibited by specific cannabinoid antagonists as well as impaired in cannabinoid receptor knock-out mice Cnr1−/−, as compared with WT mice. Thus, we propose a novel function of the endocannabinoid system, as a regulator of HSPC interactions with their BM niches, where endocannabinoids are expressed in HSC niches and under stress conditions, endocannabinoid expression levels are enhanced to induce HSPC migration for proper hematopoiesis. 相似文献
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Noy A Meyer T Rueda M Ferrer C Valencia A Pérez A de la Cruz X López-Bes JM Pouplana R Fernandez-Recio J Luque FJ Orozco M 《Journal of biomolecular structure & dynamics》2006,23(4):447-456
Analysis, storage, and transfer of molecular dynamic trajectories are becoming the bottleneck of computer simulations. In this paper we discuss different approaches for data mining and data processing of huge trajectory files generated from molecular dynamic simulations of nucleic acids. 相似文献
30.
Mycobacterium tuberculosis cells growing in macrophages are filamentous and deficient in FtsZ rings
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Chauhan A Madiraju MV Fol M Lofton H Maloney E Reynolds R Rajagopalan M 《Journal of bacteriology》2006,188(5):1856-1865
FtsZ, a bacterial homolog of tubulin, forms a structural element called the FtsZ ring (Z ring) at the predivisional midcell site and sets up a scaffold for the assembly of other cell division proteins. The genetic aspects of FtsZ-catalyzed cell division and its assembly dynamics in Mycobacterium tuberculosis are unknown. Here, with an M. tuberculosis strain containing FtsZ(TB) tagged with green fluorescent protein as the sole source of FtsZ, we examined FtsZ structures under various growth conditions. We found that midcell Z rings are present in approximately 11% of actively growing cells, suggesting that the low frequency of Z rings is reflective of their slow growth rate. Next, we showed that SRI-3072, a reported FtsZ(TB) inhibitor, disrupted Z-ring assembly and inhibited cell division and growth of M. tuberculosis. We also showed that M. tuberculosis cells grown in macrophages are filamentous and that only a small fraction had midcell Z rings. The majority of filamentous cells contained nonring, spiral-like FtsZ structures along their entire length. The levels of FtsZ in bacteria grown in macrophages or in broth were comparable, suggesting that Z-ring formation at midcell sites was compromised during intracellular growth. Our results suggest that the intraphagosomal milieu alters the expression of M. tuberculosis genes affecting Z-ring formation and thereby cell division. 相似文献