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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacillary angiomatosis (BA) and chronic bartonellosis are bacterial infections of humans which result in an unusual vascular proliferative tissue response. In order to determine their phylogenetic relationships, we have determined greater than 95% of the 16S rRNA sequences for these two organisms by amplification directly from infected BA tissue and from a Bartonella bacilliformis lyophilized culture. The BA agent and B. bacilliformis are closely related alpha-proteobacteria (98.5%), although the BA agent is more closely related to Rochalimaea quintana (99.1%). Contrary to previous belief, the BA agent is distinct from, and less closely related to, the cat scratch bacillus (Afipia felis) (90.7%). We propose a novel secondary structure in a hypervariable region of the 16S rRNA which is useful for alignment of primary sequences and which may be useful for design of nucleic acid probes.
Mol Microbiol 1992 Jul
PMID:Phylogenetic relationships among the agent of bacillary angiomatosis, Bartonella bacilliformis, and other alpha-proteobacteria. 137 24

Sbarra and Karnovsky were the first to present evidence suggesting the presence in phagocytes of a special enzyme designed to generate reactive oxidants for purposes of host defense. In the years since their report appeared, a great deal has been learned about this enzyme, now known as the respiratory burst oxidase. It has been found to be a plasma membrane-bound heme- and flavin-containing enzyme, dormant in resting cells, that catalyzes the one-electron reduction of oxygen to O2- at the expense of NADPH: O2 + NADPH----O2- + NADP+ + H+ Its behavior in whole cells and its response to various activating stimuli have been described in detail, although important insights continue to emerge, as for example a very interesting new series of observations on differences in oxidase activation patterns between suspended and adherent cells. The enzyme has been shown by biochemical and genetic studies to consist of at least six components. In the resting cell, three of these components are in the cytosol and three in the plasma membrane, but when the cell passes from its resting to its activated state the cytosolic components are all transferred to the plasma membrane, presumably assembling the oxidase. Of the components initially bound to the membrane, two constitute cytochrome b558, a heme protein characteristic of the respiratory burst oxidase, and the third may represent an oxidase flavoprotein. With regard to the cytosolic components, one is a phosphoprotein and another is the NADPH-binding component, possibly a second oxidase flavoprotein. The nature of the third (p67phox) is a puzzle. Four of the six oxidase components have now been cloned and sequenced. These findings only scratch the surface, however, and many questions remain. How many oxidase components, for example, remain to be discovered, and how do they fit together to form the active enzyme? How is the route of activation of the oxidase integrated into the general signal transduction systems of the cell? How did the oxidase come to be? Could there be a widespread system that generates small amounts of O2- as an intercellular signaling molecule, as recent work is beginning to suggest, and did the ever-destructive respiratory burst oxidase arise from that innocuous system as the creation of some evolutionary Frankenstein--an oxidase from hell? Finally, will it be possible to develop drugs that specifically block the respiratory burst oxidase, and will such drugs prove to be clinically useful as anti-inflammatory agents?(ABSTRACT TRUNCATED AT 400 WORDS)
Adv Enzymol Relat Areas Mol Biol 1992
PMID:The respiratory burst oxidase. 157 Jul 69

The method of constructing low-energy conformations using template joining can provide an efficient means of searching the conformational space of molecules. The simplest algorithm to perform this task would construct each potential conformation from scratch. However, new algorithms, some of which use techniques from Artificial Intelligence, have been developed which can greatly improve the efficiency of this approach.
J Comput Aided Mol Des 1990 Sep
PMID:Automated conformational analysis: algorithms for the efficient construction of low-energy conformations. 228 Feb 64

The SMILE program runs under MS-DOS on IBM PC AT-compatible computers equipped with the SM640 or the PG640 Matrox graphic board. The program allows real-time three-dimensional (3D) animation and modeling of several isolated molecules that can be built from scratch, manipulated interactively and compared by superimposition. SMILE enables users to compute atomic partial charges, molecular surface area, molecular volume, electrostatic and nonbonded potential energies. PLUTO, ORTEP, and MMP2 input files are set up automatically. The program also provides simple access to crystal packing by real-time animation of the unit cell contents, interactive inspection of the relevant stereochemical parameters and fragment manipulation within the unit cell. SMILE animates stereo views and produces beautiful shaded 3D images (8 colors, 32 shades each) of molecules in many different styles--stick, ball-and-stick, CPK (space filling), and transparent CPK with backbone.
J Mol Graph 1989 Sep
PMID:SMILE--shaded molecular imaging on low-cost equipment. 248 56

There is no automatic mechanism to integrate information between heterogeneous genome maps. Currently, integration is a difficult, manual process. We have developed a process for knowledge base design, and we use this to integrate order and distance relationships between genetic linkage, radiation hybrid, and physical maps. Until now, the only way to develop a persistent, knowledge-intensive application was to either develop a new knowledge base from scratch or coerce the application to fit an existing knowledge base. This was not from lack of interest by the knowledge base or database community, but merely from a lack of theoretical tools powerful enough to tackle the problem. We import formalisms from knowledge representation, natural language semantics, programming language research, and databases. These form a strong, theoretical foundation for knowledge base design upon which we have implemented the knowledge base design tool called WEAVE.
Proc Int Conf Intell Syst Mol Biol 1993
PMID:Integrating order and distance relationships from heterogeneous maps. 758 31

Thiol antioxidants are implicated in the protection of cells from oxidative injury. We studied the role of thiols in the regulation of apoptosis in cultured lung fibroblasts. Thiol depletion by culturing fibroblasts in cystine-free medium or with thiol-depleting agents induced oxidant accumulation and cell death by apoptosis. The cell death was prevented by the antioxidants ascorbic acid (AA) and catalase. Thiol depletion also induced leukotriene (LT) C4, LTD4, and LTE4 production and selective phosphorylation of p38-mitogen-activated protein kinase (MAPK) and its nuclear substrate ATF2. LT production and p38-MAPK phosphorylation were required for induction of apoptosis because thiol depletion-induced apoptosis was completely blocked by the 5-lipoxygenase inhibitor AA861, the LT antagonists FPL55712 and ONO1078, and the p38-MAPK inhibitor SB203580. LT production was inhibited by AA and p38-MAPK phosphorylation was inhibited by AA, AA861, and FPL55712. In an in vitro scratch wound model, repopulating fibroblasts at the wound margin, but not quiescent cells at the intact site, selectively underwent thiol depletion- induced apoptosis that was completely blocked by AA861, FPL55712, and SB203580. Thus, thiol depletion induces apoptosis through an ordered pathway involving oxidant accumulation, LT production, and p38-MAPK activation. Apoptosis of wound fibroblasts may be responsible for impaired wound healing in various organs, including the lung.
Am J Respir Cell Mol Biol 1999 Jul
PMID:Thiol depletion induces apoptosis in cultured lung fibroblasts. 1038 93

alpha4beta1 integrin plays an important role in cell migration. We show that when ectopically expressed in Chinese hamster ovary cells, alpha4beta1 is sufficient and required for promoting protrusion of broad lamellipodia in response to scratch-wounding, whereas alpha5beta1 does not have this effect. By time-lapse microscopy of cells expressing an alpha4/green fluorescent protein fusion protein, we show that alpha4beta1 forms transient puncta at the leading edge of cells that begin to protrude lamellipodia in response to scratch-wounding. The cells expressing a mutant alpha4/green fluorescent protein that binds paxillin at a reduced level had a faster response to scratch-wounding, forming alpha4-positive puncta and protruding lamellipodia much earlier. While enhancing lamellipodia protrusion, this mutation reduces random motility of the cells in Transwell assays, indicating that lamellipodia protrusion and random motility are distinct types of motile activities that are differentially regulated by interactions between alpha4beta1 and paxillin. Finally, we show that, at the leading edge, alpha4-positive puncta and paxillin-positive focal complexes/adhesions do not colocalize, but alpha4beta1 and paxillin colocalize partially in ruffles. These findings provide evidence for a specific role of alpha4beta1 in lamellipodia protrusion that is distinct from the motility-promoting functions of alpha5beta1 and other integrins that mediate cell adhesion and signaling events through focal complexes and focal adhesions.
Mol Biol Cell 2002 Sep
PMID:alpha4beta1 integrin regulates lamellipodia protrusion via a focal complex/focal adhesion-independent mechanism. 1222 Nov 26

Phospholipids and lipid second messengers mediate mitogenic signal transduction and oncogenesis, but there have been few successful examples of small molecules that affect biologically important phospholipid metabolism. Here we investigated the actions of a previously described antitumor agent, 4-(benzyl-(2-[(2,5-diphenyloxazole-4-carbonyl)amino]ethyl)carbamoyl)- 2-decanoylaminobutyric acid (SC-alpha alpha delta 9), which has antisignaling properties, on phospholipases. Although SC-alpha alpha delta 9 had been shown to be a potent and selective inhibitor of the Cdc25 family of dual-specificity phosphatases, many of its cellular effects are not readily reconciled with phosphatase inhibition. Molecular modeling studies suggested that SC-alpha alpha delta 9 shared several structural features with membrane phospholipids. Enzyme inhibition studies in vitro revealed that SC-alpha alpha delta 9 was a potent inhibitor of phospholipase C (PLC; IC50 = 25 microM) but did not inhibit phospholipase D activity at concentrations up to 100 microM. In H-ras (Q61L)-transformed Rat-1 fibroblasts with constitutively elevated levels of phosphorylated extracellular signal-regulated kinase (Erk), SC-alpha alpha delta 9 inhibited both proliferation and oncogenic Erk activation at concentrations that inhibited PLC in vitro. A SC-alpha alpha delta 9 congener that lacked antiproliferative activity also did not inhibit PLC in vitro. In the PLC-dependent scratch wound healing model, SC-alpha alpha delta 9 was 10-fold more potent than the phosphatidylcholine-specific PLC inhibitor D-609. We propose that the structural resemblance of SC-alpha alpha delta 9 to phospholipids allows it to inhibit cellular PLC, thereby providing a possible molecular mechanism for SC-alpha alpha delta 9's effects on oncogenic Erk activation.
Mol Cancer Ther 2002 Sep
PMID:The antisignaling agent SC-alpha alpha delta 9, 4-(benzyl-(2-[(2,5-diphenyloxazole-4-carbonyl)amino]ethyl)carbamoyl)- 2-decanoylaminobutyric acid, is a structurally unique phospholipid analogue with phospholipase C inhibitory activity. 1248 9

Human SNAIL1 (SNAI1) protein encoded by SNAI1/SNA gene represses transcription of E-cadherin/CDH1 gene. Human SNAIL2 (SNAI2) protein encoded by SNAI2/SLUG gene induces the first phase of epithelial-mesenchymal transition (EMT), including desmosome dissociation, cell spreading, and initiation of cell separation. Here, we have identified human SNAIL3 (SNAI3) gene using bioinformatics. Human SNAI3 gene, consisting of at least three exons, spans around the nucleotide position 320214-328221 of human reference genomic contig NT_010404.8 in the reverse orientation. SNAI3 gene, was located between KIAA0233 gene and CBFA2T3 gene in human chromosome 16q24.3, a region affected in breast cancer, gastric cancer, hepatocellular carcinoma, ovarian cancer, and therapy-related myeloid leukemia with t(16;21)(q24;q22) translocation. Human SNAI3 gene was found to encode 292-amino-acid polypeptide with the N-terminal SNAG domain and five zinc finger domains. N-terminal SNAG domain was identified in zinc finger proteins SNAI1, SNAI2, SNAI3, SCRATCH (SCRT1), GFI1, and GFI1B. ATP/GTP binding site was identified in SCRT1, GFI1 and GFI1B, but not in SNAI1, SNAI2 and SNAI3. Phylogenetic analysis of human zinc finger proteins with SNAG domain revealed that SNAI1, SNAI2 and SNAI3 were more closely related. These results clearly indicate that SNAI1, SNAI2 and SNAI3 constitute a subfamily among SNAG zinc-finger proteins. Human SNAI3 mRNA was expressed in skin melanotic melanoma, lung epidermoid carcinoma, and germ cell tumor. Because SNAG zinc-finger proteins are transcriptional repressors implicated in carcinogenesis and embryogenesis, SNAI3 gene might be a potent target of pharmacogenomics in the field of oncology and regenerative medicine.
Int J Mol Med 2003 Mar
PMID:Identification and characterization of human SNAIL3 (SNAI3) gene in silico. 1257 45

Cell motility and cell polarity are essential for morphogenesis, immune system function, and tissue repair. Many animal cells move by crawling, and one main driving force for movement is derived from the coordinated assembly and disassembly of actin filaments. As tissue culture cells migrate to close a scratch wound, this directional extension is accompanied by Golgi apparatus reorientation, to face the leading wound edge, giving the motile cell inherent polarity aligned relative to the wound edge and to the direction of cell migration. Cellular proteins essential for actin polymerization downstream of Rho family GTPases include the Arp2/3 complex as an actin nucleator and members of the Wiskott-Aldrich Syndrome protein (WASP) family as activators of the Arp2/3 complex. We therefore analyzed the involvement of the Arp2/3 complex and WASP-family proteins in in vitro wound healing assays using NIH 3T3 fibroblasts and astrocytes. In NIH 3T3 cells, we found that actin and Arp2/3 complex contributed to cell polarity establishment. Moreover, overexpression of N-terminal fragments of Scar2 (but not N-WASP or Scar1 or Scar3) interfere with NIH 3T3 Golgi polarization but not with cell migration. In contrast, actin, Arp2/3, and WASP-family proteins did not appear to be involved in Golgi polarization in astrocytes. Our results thus indicate that the requirement for Golgi polarity establishment is cell-type specific. Furthermore, in NIH 3T3 cells, Scar2 and the Arp2/3 complex appear to be involved in the establishment and maintenance of Golgi polarity during directed migration.
Mol Biol Cell 2003 Feb
PMID:Involvement of the Arp2/3 complex and Scar2 in Golgi polarity in scratch wound models. 1258 62


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