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Models for the spatial distribution of protein, lipid and water in gap junction structures have been constructed from the results of the analysis of X-ray diffraction data described here and the electron microscope and chemical data presented in the preceding paper (Caspar, D. L. D., D. A. Goodenough, L. Makowski, and W.C. Phillips. 1977. 74:605-628). The continuous intensity distribution on the meridian of the X-ray diffraction pattern was measured, and corrected for the effects of the partially ordered stacking and partial orientation of the junctions in the X-ray specimens. The electron density distribution in the direction perpendicular to the plane of the junction was calculated from the meridional intensity data. Determination of the interference function for the stacking of the junctions improved the accuracy of the electron density profile. The pair-correlation function, which provides information about the packing of junctions in the specimen, was calculated from the interference function. The intensities of the hexagonal lattice reflections on the equator of the X-ray pattern were used in coordination with the electron microscope data to calculate to the two-dimensional electron density projection onto the plane of the membrane. Differences in the structure of the connexons as seen in the meridional profile and equatorial projections were shown to be correlated to changes in lattice constant. The parts of the junction structure which are variable have been distinguished from the invariant parts by comparison of the X-ray data from different specimens. The combination of these results with electron microscope and chemical data provides low resolution three- dimensional representations of the structures of gap junctions. 相似文献
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The role of nitric oxide in cancer 总被引:4,自引:0,他引:4
WEIMING XU Li ZHI LIU MARILENA LOIZIDOU MOHAMED AHMED IAN G CHARLES Wolfson Institute for Biomedical Research Cruciform Building Gower Street UCL London WC E AUUK Department of Surgery Charles Bell House - Riding House Street UCL London WW EJ UK 《Cell research》2002,(Z2)
Nitric oxide (NO) is a pleiotropic regulator, critical to numerous biological processes, including va-sodilatation, neurotransmission and macrophage-mediated immunity. The family of nitric oxide synthases (NOS) comprises inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Interestingly, various studies have shown that all three isoforms can be involved in promoting or inhibiting the etiology of cancer. NOS activity has been detected in tumour cells of various histogenetic origins and has been associated with tumour grade, proliferation rate and expression of important signaling components associated with cancer development such as the oestrogen receptor. It appears that high levels of NOS expression (for example, generated by activated macrophages) may be cytostatic or cytotoxic for tumor cells, whereas low level activity can have the opposite effect and promote tumour growth. Paradoxically therefore, NO (and related reactive nitrogen species) may have both genotoxic and angiogenic pro 相似文献
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Mi Young YangAmit Chaudhary Steven SeamanJill Dunty Janine StevensMohammed K. Elzarrad Arthur E. FrankelBrad St. Croix 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(1):39-49
Tumor endothelial marker 8 (TEM8) is an integrin-like cell surface protein upregulated on tumor blood vessels and a potential vascular target for cancer therapy. Here, we found that the ability of an anti-TEM8 antibody, clone SB5, to recognize the extracellular domain of TEM8 on the cell surface depends on other host-cell factors. By taking advantage of SB5's ability to distinguish different forms of cell surface TEM8, we identified alpha-smooth muscle actin and transgelin, an actin binding protein, as intracellular factors able to alter TEM8 cell surface structure. Overexpression of either of these proteins in cells converted TEM8 from an SB5-exposed to an SB5-masked form and protected cells from SB5-saporin immunotoxins. Because the predominant form of TEM8 on the cell surface is not recognized by SB5, we also developed a new monoclonal antibody, called AF334, which is able to recognize both the SB5-exposed and the SB5-masked forms of TEM8. AF334-saporin selectively killed TEM8-positive cells independent of TEM8 cell surface structure. These studies reveal that TEM8 exists in different forms at the cell surface, a structure dependent on interactions with components of the actin cytoskeleton, and should aid in the rational design of the most effective diagnostic and therapeutic anti-TEM8 monoclonal antibodies. 相似文献
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Paired sequence difference in ribosomal RNAs: evolutionary and phylogenetic implications 总被引:12,自引:1,他引:11
Ribosomal RNAs have secondary structures that are maintained by internal
Watson-Crick pairing. Through analysis of chordate, arthropod, and plant 5S
ribosomal RNA sequences, we show that Darwinian selection operates on these
nucleotide sequences to maintain functionally important secondary
structure. Insect phylogenies based on nucleotide positions involved in
pairing and the production of secondary structure are incongruent with
those constructed on the basis of positions that are not. Furthermore,
phylogeny reconstruction using these nonpairing bases is concordant with
other, morphological data.
相似文献
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The focal adhesion kinase (FAK) and cell adhesion kinase beta (CAKbeta, PYK2, CADTK, RAFTK) are highly homologous FAK family members, yet clearly have unique roles in the cell. Comparative analyses of FAK and CAKbeta have revealed intriguing differences in their activities. These differences were investigated further through the characterization of a set of FAK/CAKbeta chimeric kinases. CAKbeta exhibited greater catalytic activity than FAK in vitro, providing a molecular basis for differential substrate phosphorylation by FAK and CAKbeta in vivo. Furthermore, the N terminus may regulate catalytic activity since chimeras containing the FAK N terminus and CAKbeta catalytic domain exhibited a striking high level of catalytic activity and substrate phosphorylation. Unexpectedly, a modulatory role for the N termini in subcellular localization was also revealed. Chimeras containing the FAK N terminus and CAKbeta C terminus localized to focal adhesions, whereas chimeras containing the N and C termini of CAKbeta did not. Finally, prominent changes in cell morphology were induced upon expression of chimeras containing the CAKbeta N terminus, which were not associated with apoptotic cell death, cell cycle progression delay, or changes in Rho activity. These results demonstrate novel regulatory roles for the N terminus of FAK family kinases. 相似文献
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Mitochondrial gene order is not conserved in arthropods: prostriate and metastriate tick mitochondrial genomes 总被引:25,自引:15,他引:10
The entire mitochondrial genome was sequenced in a prostriate tick, Ixodes
hexagonus, and a metastriate tick, Rhipicephalus sanguineus. Both genomes
encode 22 tRNAs, 13 proteins, and two ribosomal RNAs. Prostriate ticks are
basal members of Ixodidae and have the same gene order as Limulus
polyphemus. In contrast, in R. sanguineus, a block of genes encoding NADH
dehydrogenase subunit 1 (ND1), tRNA(Leu)(UUR), tRNA(Leu)(CUN), 16S rDNA,
tRNA(Val), 12S rDNA, the control region, and the tRNA(Ile) and tRNA(Gln)
have translocated to a position between the tRNA(Glu) and tRNA(Phe) genes.
The tRNA(Cys) gene has translocated between the control region and the
tRNA(Met) gene, and the tRNA(Leu)(CUN) gene has translocated between the
tRNA(Ser)(UCN) gene and the control region. Furthermore, the control region
is duplicated, and both copies undergo concerted evolution. Primers that
flank these rearrangements confirm that this gene order is conserved in all
metastriate ticks examined. Correspondence analysis of amino acid and codon
use in the two ticks and in nine other arthropod mitochondrial genomes
indicate a strong bias in R. sanguineus towards amino acids encoded by
AT-rich codons.
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