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Mark AJ Roberts Elias August Abdullah Hamadeh Philip K Maini Patrick E McSharry Judith P Armitage Antonis Papachristodoulou 《BMC systems biology》2009,3(1):105-14
Background
Developing methods for understanding the connectivity of signalling pathways is a major challenge in biological research. For this purpose, mathematical models are routinely developed based on experimental observations, which also allow the prediction of the system behaviour under different experimental conditions. Often, however, the same experimental data can be represented by several competing network models. 相似文献3.
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14-3-3 proteins are intracellular, dimeric molecules that bind to and modify the activity of several signaling proteins. We used human 14-3-3zeta as a bait in the yeast two-hybrid system to screen a murine embryonic cDNA library. One interacting clone was found to encode the carboxyl terminus of a putative protein kinase. The coding sequence of the human form (protein kinase Ualpha, PKUalpha) of this protein kinase was found in GenBank(TM) on the basis of sequence homology. The two-hybrid clone was also highly homologous to TOUSLED, an Arabidopsis thaliana protein kinase that is required for normal flower and leaf development. PKUalpha has been found by coimmunoprecipitation to bind to 14-3-3zeta in vivo. Our confocal laser immunofluorescence microscopic experiments revealed that PKUalpha colocalizes with the cytoplasmic intermediate filament system of cultured fibroblasts in the G(1) phase of the cell cycle. PKUalpha is found in the perinuclear area of S phase cells and in the nucleus of late G(2) cells. Transfection of cells with a dominant negative form of 14-3-3eta promotes the nuclear localization of PKUalpha. These results suggest that the subcellular localization of PKUalpha is regulated, at least in part, by its association with 14-3-3. 相似文献
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Rates and patterns of evolution in partial sequences of five mitochondrial
genes (cytochrome b, ATPase 6, NADH dehydrogenase subunit 5, tRNA(Glu), and
the control region) were compared among taxa in the passerine bird genera
Fringilla and Carduelis. Rates of divergence do not vary significantly
among genes, even in comparisons with the control region. Rate variation
among lineages is significant only for the control region and NADH
dehydrogenase subunit 5, and patterns of variation are consistent with the
expectations of neutral theory. Base composition is biased in all genes but
is stationary among lineages, and there is evidence for directional
mutation pressure only in the control region. Despite these similarities,
patterns of substitution differ among genes, consistent with alternative
regimes of selective constraint. Rates of nonsynonymous substitution are
higher in NADH dehydrogenase subunit 5 than in other protein-coding genes,
and transitions exist in elevated proportions relative to transversions.
Transitions appear to accumulate linearly with time in tRNA(Glu), and
despite exhibiting the highest overall rate of divergence among species,
there are no transversional changes in this gene. Finally, for resolving
phylogenetic relationships among Fringilla taxa, the combined
protein-coding data are broadly similar to those of the control region in
terms of phylogenetic informativeness and statistical support.
相似文献
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BiP and calreticulin form an abundant complex that is independent of endoplasmic reticulum stress 总被引:5,自引:1,他引:4 下载免费PDF全文
BiP is found in association with calreticulin, both in the presence and absence of endoplasmic reticulum stress. Although the BiP-calreticulin complex can be disrupted by ATP, several properties suggest that the calreticulin associated with BiP is neither unfolded nor partially or improperly folded. (1) The complex is stable in vivo and does not dissociate during 8 hr of chase. (2) When present in the complex, calreticulin masks epitopes at the C terminus of BiP that are not masked when BiP is bound to an assembly-defective protein. And (3) overproduction of calreticulin does not lead to the recruitment of more BiP into complexes with calreticulin. The BiP-calreticulin complex can be disrupted by low pH but not by divalent cation chelators. When the endoplasmic reticulum retention signal of BiP is removed, complex formation with calreticulin still occurs, and this explains the poor secretion of the truncated molecule. Gel filtration experiments showed that BiP and calreticulin are present in distinct high molecular weight complexes in which both molecules interact with each other. The possible functions of this complex are discussed. 相似文献
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Black AP Bhayani H Ryder CA Pugh MT Gardner-Medwin JM Southwood TR 《Arthritis research & therapy》2003,5(5):R277-R284
The aim of this research was to determine whether all memory T cells have the same propensity to migrate to the joint in patients
with juvenile idiopathic arthritis. Paired synovial fluid and peripheral blood mononuclear cell proliferative responses to
a panel of antigens were measured and the results correlated with a detailed set of laboratory and clinical data from 39 patients
with juvenile idiopathic arthritis. Two distinct patterns of proliferative response were found in the majority of patients:
a diverse pattern, in which synovial fluid responses were greater than peripheral blood responses for all antigens tested;
and a restricted pattern, in which peripheral blood responses to some antigens were more vigorous than those in the synovial
fluid compartment. The diverse pattern was generally found in patients with a high acute phase response, whereas patients
without elevated acute phase proteins were more likely to demonstrate a restricted pattern. We propose that an association
between the synovial fluid T cell repertoire and the acute phase response suggests that proinflammatory cytokines may influence
recruitment of memory T cells to an inflammatory site, independent of their antigen specificity. Additionally, increased responses
to enteric bacteria and the presence of αEβ7 T cells in synovial fluid may reflect accumulation of gut associated T cells
in the synovial compartment, even in the absence of an elevated acute phase response. This is the first report of an association
between the acute phase response and the T cell population recruited to an inflammatory site. 相似文献
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