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Results for “Integrative interaction”

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At least 1,009 records · Page 56Linked to original sources

PubMed2006

Integrative study of hypothalamus-pituitary-thyroid-immune system interaction: thyroid hormone-mediated modulation of lymphocyte activity through the protein kinase C signaling pathway.

Thyroid hormones play critical roles in differentiation, growth and metabolism, but their participation in immune system regulation has not been completely elucidated. Modulation of in vivo thyroid status was used to carry out an integrative analysis of the role of the hypothalamus-pituitary-thyroid (HPT) axis in T and B lymphocyte activity. The participation of the protein kinase C (PKC) signaling pathway and the release of some cytokines upon antigenic stimulation were analyzed. Lymphocytes from hyperthyroid mice displayed higher T-and B-cell mitogen-induced proliferation, and those from hypothyroid mice displayed lower T- and B-cell mitogen-induced proliferation, compared with euthyroid animals. Reversion of hypothyroid state by triiodothyronine (T3) administration recovered the proliferative responses. No differences were found in lymphoid subset balance. Both total PKC content and mitogen-induced PKC translocation were higher in T and B cells from hyperthyroid mice, and lower in cells from hypothyroid mice, compared with controls. Levels of thyroid-stimulating (TSH) and TSH-releasing (TRH) hormones were not directly related to lymphocyte proliferative responses. After immunization with sheep red blood cells (SRBCs) and re-stimulation, in vitro spleen cells from hyper- or hypothyroid mice showed, respectively, increased or decreased production of interleukin (IL)-2 and interferon (IFN)-gamma cytokines. Additionally, an increase in IL-6 and IFN-gamma levels was found in hyperthyroid cells after in vivo injection and in vitro re-stimulation with lipopolysaccharide (LPS). Our results show for the first time a thyroid hormone-mediated regulation of PKC content and of cytokine production in lymphocytes; this regulation could be involved in the altered responsiveness to mitogen-induced proliferation of T and B cells. The results also confirm the important role that these hormones play in regulating lymphocyte reactivity.

Animals↗

PubMed1988

Interaction of fibronectin with DNA/anti-DNA complexes from systemic lupus erythematosus: role of activated complement Cl in modulation of the interactions.

Fibronectin (Fn) is an integral constituent of the endothelial cell surface and the basement membrane. The mechanism for binding DNA/anti-DNA complexes to Fn was examined in a solid-phase assay. In physiological buffer, a low-affinity binding of DNA was observed with Fn and optimal binding was seen at pH 6.5 and in the absence of Ca2+. Further, the interaction of DNA to Fn was inhibited when DNA was complexed to anti-DNA antibody. However, complement Clq mediated the binding of complexes to Fn at pH 7.4 and it was proportional to the extent of the dissociation of Cl. Cl inactivator (Cl-In) appeared to play a modulating role; whereas at low concentrations (Cl:Cl-In::4: less than 1) it enhanced the binding of complexes to Fn, higher concentrations inhibited the binding. Further, sera from patients with active systemic lupus erythematosus reacted with Fn, which was shown to be dependent on the presence of Clq and was minimally affected by DNase treatment of sera, indicating a relatively minor role of DNA in the direct binding of DNA to Fn. These findings support "circulating immune complex" hypothesis in the pathogenesis of lupus glomerular immune complex deposition disease.

Antibodies, Antinuclear↗

PubMed1999

Three-wave interaction in two-component quadratic nonlinear lattices.

We investigate a two-component lattice with a quadratic nonlinearity and find with the multiple scale technique that integrable three-wave interaction takes place between plane wave solutions when these fulfill resonance conditions. We demonstrate that energy conversion and pulse propagation known from three-wave interaction is reproduced in the lattice and that exact phase matching of parametric processes can be obtained in non-phase-matched lattices by tilting the interacting plane waves with respect to each other.

Journal Article↗

PubMed2003

Substrate specificity of type III flagellar protein export in Salmonella is controlled by subdomain interactions in FlhB.

FlhB, an integral membrane protein, gates the type III flagellar export pathway of Salmonella. It permits export of rod/hook-type proteins before hook completion, whereupon it switches specificity to recognize filament-type proteins. The cytoplasmic C-terminal domain of FlhB (FlhBC) is cleaved between Asn-269 and Pro-270, defining two subdomains: FlhBCN and FlhBCC. Here, we show that subdomain interactions and cleavage within FlhB are central to substrate-specificity switching. We found that deletions between residues 216 and 240 of FlhBCN permitted FlhB cleavage but abolished function, whereas a deletion spanning Asn-269 and Pro-270 abolished both. The mutation N269A prevented cleavage at the FlhBCN-FlhBCC boundary. Cells producing FlhB(N269A) exported the same amounts of hook-capping protein as cells producing wild-type FlhB. However, they exported no flagellin, even when the fliC gene was being expressed from a foreign promoter to circumvent regulation of expression by FlgM, which is itself a filament-type substrate. Electron microscopy revealed that these cells assembled polyhook structures lacking filaments. Thus, FlhB(N269A) is locked in a conformation specific for rod/hook-type substrates. With FlhB(P270A), cleavage was reduced but not abolished, and cells producing this protein were weakly motile, exported reduced amounts of flagellin and assembled polyhook filaments.

Bacterial Proteins↗

PubMed1998

Photo-cross-linking studies suggest a model for the architecture of an active human immunodeficiency virus type 1 integrase-DNA complex.

The virally encoded integrase protein carries out retroviral integration, which requires specific interactions with the two ends of the viral DNA, and also with host DNA that is the target of integration. We attached a photo-cross-linking agent to specific viral and target DNA sites to identify regions of the integrase polypeptide that are in close proximity to those substrate features in the active integrase-DNA complex. The active form of integrase is a multimer. The higher-order organization of the active integration complex was therefore investigated by determining whether specific cross-links occurred to the active-site containing protomer. Both viral and target DNA cross-links to human immunodeficiency virus type 1 (HIV-1) integrase mapped predominantly to integrase protomers in trans to the active site, in a multimeric integrase complex. The results provide the basis for a model of the protein-DNA architecture of an active HIV-1 integration complex that suggests specific functions for the N-terminal, core, and C-terminal domains of retroviral integrase. One implication of this model is that the integrase multimer that mediates concerted integration of the viral DNA ends is composed of at least eight integrase protomers.

Catalysis↗

PubMed1994

Integrating with integrins.

Our central claim is that signaling by integrins provides a mechanism by which signals generated in response to adhesion, soluble hormones, and mechanical forces can interact. Such interactions permit cells to integrate these different classes of external stimuli and hence to orchestrate an efficient response. This integrating function of integrins is likely to be essential for much of development and physiology, as well as complex pathologies such as cancer. Understanding in detail how these signals are transduced and processed is likely to be an important area of research in the near future.

Animals↗

PubMed2005

Atlas - a data warehouse for integrative bioinformatics.

BACKGROUND: We present a biological data warehouse called Atlas that locally stores and integrates biological sequences, molecular interactions, homology information, functional annotations of genes, and biological ontologies. The goal of the system is to provide data, as well as a software infrastructure for bioinformatics research and development. DESCRIPTION: The Atlas system is based on relational data models that we developed for each of the source data types. Data stored within these relational models are managed through Structured Query Language (SQL) calls that are implemented in a set of Application Programming Interfaces (APIs). The APIs include three languages: C++, Java, and Perl. The methods in these API libraries are used to construct a set of loader applications, which parse and load the source datasets into the Atlas database, and a set of toolbox applications which facilitate data retrieval. Atlas stores and integrates local instances of GenBank, RefSeq, UniProt, Human Protein Reference Database (HPRD), Biomolecular Interaction Network Database (BIND), Database of Interacting Proteins (DIP), Molecular Interactions Database (MINT), IntAct, NCBI Taxonomy, Gene Ontology (GO), Online Mendelian Inheritance in Man (OMIM), LocusLink, Entrez Gene and HomoloGene. The retrieval APIs and toolbox applications are critical components that offer end-users flexible, easy, integrated access to this data. We present use cases that use Atlas to integrate these sources for genome annotation, inference of molecular interactions across species, and gene-disease associations. CONCLUSION: The Atlas biological data warehouse serves as data infrastructure for bioinformatics research and development. It forms the backbone of the research activities in our laboratory and facilitates the integration of disparate, heterogeneous biological sources of data enabling new scientific inferences. Atlas achieves integration of diverse data sets at two levels. First, Atlas stores data of similar types using common data models, enforcing the relationships between data types. Second, integration is achieved through a combination of APIs, ontology, and tools. The Atlas software is freely available under the GNU General Public License at: http://bioinformatics.ubc.ca/atlas/

Computational Biology↗

PubMed2002

Activation of the repulsive receptor Roundabout inhibits N-cadherin-mediated cell adhesion.

The formation of axon trajectories requires integration of local adhesive interactions with directional information from attractive and repulsive cues. Here, we show that these two types of information are functionally integrated; activation of the transmembrane receptor Roundabout (Robo) by its ligand, the secreted repulsive guidance cue Slit, inactivates N-cadherin-mediated adhesion. Loss of N-cadherin-mediated adhesion is accompanied by tyrosine phosphorylation of beta-catenin and its loss from the N-cadherin complex, concomitant with the formation of a supramolecular complex containing Robo, Abelson (Abl) kinase and N-cadherin. Local formation of such a receptor complex is an ideal mechanism to steer the growth cone while still allowing adhesion and growth in other directions.

Animals↗

PubMed2007

Qualitative network models and genome-wide expression data define carbon/nitrogen-responsive molecular machines in Arabidopsis.

BACKGROUND: Carbon (C) and nitrogen (N) metabolites can regulate gene expression in Arabidopsis thaliana. Here, we use multi-network analysis of microarray data to identify molecular networks regulated by C and N in the Arabidopsis root system. RESULTS: We used the Arabidopsis whole genome Affymetrix gene chip to explore global gene expression responses in plants exposed transiently to a matrix of C and N treatments. We used ANOVA analysis to define quantitative models of regulation for all detected genes. Our results suggest that about half of the Arabidopsis transcriptome is regulated by C, N or CN interactions. We found ample evidence for interactions between C and N that include genes involved in metabolic pathways, protein degradation and auxin signaling. To provide a global, yet detailed, view of how the cell molecular network is adjusted in response to the CN treatments, we constructed a qualitative multi-network model of the Arabidopsis metabolic and regulatory molecular network, including 6,176 genes, 1,459 metabolites and 230,900 interactions among them. We integrated the quantitative models of CN gene regulation with the wiring diagram in the multi-network, and identified specific interacting genes in biological modules that respond to C, N or CN treatments. CONCLUSION: Our results indicate that CN regulation occurs at multiple levels, including potential post-transcriptional control by microRNAs. The network analysis of our systematic dataset of CN treatments indicates that CN sensing is a mechanism that coordinates the global and coordinated regulation of specific sets of molecular machines in the plant cell.

Arabidopsis↗

PubMed1996

Conserved amino acids in the N- and C-terminal domains of integral membrane transporter FhuB define sites important for intra- and intermolecular interactions.

Transport of iron(III) hydroxamates across the inner membrane of Escherichia coli is mediated by a peri-plasmic binding protein-dependent transport (PBT) mechanism. FhuB, the integral membrane component of the system, is composed of covalently linked halves (FhuB[N] and FhuB[C]) which still function when present as two distinct polypeptide chains. Our analysis of two uptake-deficient FhuB derivatives provides evidence for a mechanistically novel type of functional complementation: 'domain displacement' in the cyto-plasmic membrane. Amino acid residues 60 and 426 in the FhuB polypeptide chain may define key positions that are important for FhuB[N]-FhuB[C] interaction. Furthermore, FhuB derivatives, altered in either one of their conserved regions--typical of PBT related integral membrane proteins--displayed a dominant negative effect on ferric hydroxamate transport. The experimental data suggest that the two functionally equivalent conserved regions in FhuB[N] and FhuB[C] are primarily involved in the interaction with another component of the transport system, probably FhuC.

ATP-Binding Cassette Transporters↗

PubMed1987

Effects of carotid artery occlusion on the pressor response induced by sustained isometric contraction in the cat.

The effects of clonidine, a central alpha 2 agonist, on changes in blood pressure caused by muscle afferent nerve (ergoreceptor) activation and baroreceptor manipulation were studied in cats. Prolonged isometric contractions (ergoreceptor activation) of the gastrocnemius and plantaris muscles increased mean arterial pressure by 53 mmHg. This pressor response was not altered by naloxone (0.5 mumol.litre-1) but was eliminated by clonidine (0.5-2.0 micrograms) when injected into the cerebral aqueduct. Brief occlusion of the carotid artery (15-30 s) caused mean arterial pressure to increase by 32-42 mmHg at rest. Neither naloxone nor clonidine altered the magnitude of the reflex pressor response to carotid occlusion. Similar increases in pressure were measured when occlusion was applied during fatiguing isometric contractions; thus baroreceptor induced increases in pressure were superimposed on the ergoreceptor induced blood pressure changes. Naloxone did not affect the changes in pressure caused by either reflex response. Clonidine continued to eliminate the pressor response to muscular contraction but did not affect the pressure increase when the carotid occlusion was applied during contractions. Electrical stimulation of the carotid sinus nerve caused blood pressure to decrease by 36 mmHg during rest and by 41 mmHg during fatiguing isometric contractions. Clonidine did not alter the depressor response to carotid sinus nerve stimulation. These data may indicate that separate pathways centrally mediate the changes in blood pressure caused by ergoreceptor and baroreceptor afferent activation. The integration of the ergoreceptor pathway may involve a catecholaminergic-opioidergic system but the present results do not suggest a similar interaction for the baroreceptor integration.

Animals↗

PubMed1987

Integrating ancient and modern medicine in Chinese hospitals. The interaction among technology, traditional Chinese medicine, and health care.

Modern industrial society and its industrial processes can sometimes discourage the practice of traditional medicine. The existence and use of traditional Chinese medicine for several thousands of years indicates that it has sound elements. As has been true with features of other ancient, highly developed civilizations, the discipline of traditional Chinese medicine offers a valuable resource in the treatment and prevention of disease. Its scientific aspects and valuable experiences must continue to be developed according to Western scientific methodology. China has initiated a program to utilize modern industrialized technology in the integration of the traditional Chinese and modern Western medical systems. The policy and process aimed at integrating traditional Chinese medicine with Western medicine are presented in this paper. These measures have resulted in considerable utilization and development of the traditional Chinese medicine system, and have had a major impact on the development of public health care, as well as medical technology and science. The positive interactions between these fields of study and existing problems are discussed, and some comments on future expectations are presented.

China↗

PubMed1996

Novel proteins that interact with the COOH-terminal cytosolic routing determinants of an integral membrane peptide-processing enzyme.

The steady state distribution of membrane forms of peptidylglycine alpha-amidating monooxygenase (PAM) in the secretory pathway of neurons and endocrine cells depends on signals in its cytosolic COOH-terminal domain (CD). Mutagenesis studies yielded catalytically active PAM proteins that are not properly localized or internalized. Employing the yeast two-hybrid system, we isolated two distinct cDNAs whose protein products showed a strong interaction with the CD of PAM. The interaction of these novel PAM COOH-terminal interactor proteins (P-CIPs) did not occur with a misrouted CD mutant as bait in the yeast system. Both proteins, P-CIP2 and P-CIP10, were expressed as fusion proteins that interacted in vitro with solubilized integral membrane PAM. P-CIP2 was homologous to several serine/threonine and dual specificity protein kinases, while P-CIP10 contained spectrin-like repeats. Endogenous P-CIP2 was localized to the Golgi region of AtT-20 corticotrope tumor cells, and expression of integral membrane PAM disrupted the distribution of endogenous P-CIP2. Both P-CIP2 and P-CIP10 mRNAs were found to be expressed in rat brain neurons also expressing PAM proteins. P-CIP2 and P-CIP10 may be members of a family of cytosolic proteins involved in the routing of membrane proteins that function in the regulated secretory pathway.

Amino Acid Sequence↗

PubMed1990

Lipid-protein interactions in membranes.

The interactions of lipids with integral and peripheral proteins can be studied in reconstituted and natural membranes using spin label electron spin resonance (ESR) spectroscopy. The ESR spectra reveal a reduction in mobility of the spin-labelled lipid species, and in certain cases evidence is obtained for a partial penetration of the peripheral proteins into the membrane. The latter may be relevant to the import mechanism of apocytochrome c into mitochondria. Integral proteins induce a more direct motional restriction of the spin-labelled lipid chains, allowing the stoichiometry and specificity of the interaction, and the lipid exchange rate at the protein interface to be determined from the ESR spectra. In this way, a population of very slowly exchanging cardiolipin associated with the mitochondrial ADP-ATP carrier has been identified. The residues involved in the specificity for charged lipids of the myelin proteolipid protein have been localized to the deletion in the DM-20 mutant, and the difference in lipid-protein interactions with the beta-sheet and alpha-helical conformations of the M-13 coat protein, has been characterized.

Cell Membrane↗

PubMed2003

The twin-arginine leader-binding protein, DmsD, interacts with the TatB and TatC subunits of the Escherichia coli twin-arginine translocase.

The twin-arginine translocase (Tat) pathway is involved in the targeting and translocation of fully folded proteins to the inner membrane and periplasm of bacteria. Proteins that use this pathway contain a characteristic twin-arginine signal sequence, which interacts with the receptor complex formed by the TatBC subunits. Recently, the DmsD protein was discovered, which binds to the twin-arginine signal sequences of the anaerobic respiratory enzymes dimethylsulfoxide reductase (DmsABC) and trimethylamine N-oxide (TMAO) reductase. In this work, the targeting of DmsD within Escherichia coli was investigated. Using cell fractionation and Western blot analysis, DmsD is found to be associated with the inner membrane of wild-type E. coli and a dmsABC mutant E. coli under anaerobic conditions. In contrast, DmsD is predominantly found in the cytoplasmic fraction of a Delta tatABCDE strain, which suggests that DmsD interacts with the membrane-associated Tat complex. Under aerobic conditions DmsD was also found primarily in the cytoplasmic fraction of wild-type E. coli, suggesting that physiological conditions have a significant effect upon the targeting of DmsD to the inner membrane. Size exclusion chromatography data and membrane washing studies indicate that DmsD is interacting tightly with an integral membrane protein and not with the lipid component of the E. coli inner membrane. Additional investigation into the nature of this interaction revealed that the TatB and TatC subunits of the translocase are important for the interaction of DmsD with the E. coli inner membrane.

Blotting, Western↗

PubMed2002

Automated modelling of signal transduction networks.

BACKGROUND: Intracellular signal transduction is achieved by networks of proteins and small molecules that transmit information from the cell surface to the nucleus, where they ultimately effect transcriptional changes. Understanding the mechanisms cells use to accomplish this important process requires a detailed molecular description of the networks involved. RESULTS: We have developed a computational approach for generating static models of signal transduction networks which utilizes protein-interaction maps generated from large-scale two-hybrid screens and expression profiles from DNA microarrays. Networks are determined entirely by integrating protein-protein interaction data with microarray expression data, without prior knowledge of any pathway intermediates. In effect, this is equivalent to extracting subnetworks of the protein interaction dataset whose members have the most correlated expression profiles. CONCLUSION: We show that our technique accurately reconstructs MAP Kinase signaling networks in Saccharomyces cerevisiae. This approach should enhance our ability to model signaling networks and to discover new components of known networks. More generally, it provides a method for synthesizing molecular data, either individual transcript abundance measurements or pairwise protein interactions, into higher level structures, such as pathways and networks.

Computational Biology↗

PubMed2003

Kinase pathway database: an integrated protein-kinase and NLP-based protein-interaction resource.

Protein kinases play a crucial role in the regulation of cellular functions. Various kinds of information about these molecules are important for understanding signaling pathways and organism characteristics. We have developed the Kinase Pathway Database, an integrated database involving major completely sequenced eukaryotes. It contains the classification of protein kinases and their functional conservation, ortholog tables among species, protein-protein, protein-gene, and protein-compound interaction data, domain information, and structural information. It also provides an automatic pathway graphic image interface. The protein, gene, and compound interactions are automatically extracted from abstracts for all genes and proteins by natural-language processing (NLP). The method of automatic extraction uses phrase patterns and the GENA protein, gene, and compound name dictionary, which was developed by our group. With this database, pathways are easily compared among species using data with more than 47,000 protein interactions and protein kinase ortholog tables. The database is available for querying and browsing at http://kinasedb.ontology.ims.u-tokyo.ac.jp/.

Animals↗

PubMed1990

Protein zero of peripheral nerve myelin: biosynthesis, membrane insertion, and evidence for homotypic interaction.

Protein zero (P0), an integral membrane glycoprotein synthesized by Schwann cells, is the major glycoprotein of peripheral nerve myelin. The predicted disposition of P0 with respect to the membrane bilayer postulates the existence of extracellular and intracellular domains, that mediate compaction of the myelin lamellae. We used in vitro translations programmed with sciatic nerve mRNA and cells transfected with a P0 cDNA construct to study the biosynthesis and topology of P0 in the bilayer. The behavior of P0 at the cell surface, when expressed under physiological conditions, was also examined. We have verified the topological predictions of an earlier model, derived from analysis of a P0 cDNA, and provide evidence that the extracellular domain of P0 mediates homotypically cell-cell interactions in the transfectants.

Amino Acid Sequence↗