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Signal transduction in cells of the immune system in microgravity
Oliver Ullrich, Kathrin Huber, Kerstin Lang
Cell Communication and Signaling , 2008, DOI: 10.1186/1478-811x-6-9
Abstract: Early reports about disturbed immune cell function in space date back in the 70ties, where reduced reactivity of blood lymphoid cells has been discovered in crew members of Soyuz spaceships and of Skylab and Apollo [1,2]. Recently, a subclinical re-activation varicella zoster virus (VZV) has been reported in astronauts [3,4], a virus which becomes latent in the nervous system after primary infection, but is reactivated frequently in immune suppressed individuals, such as after organ transplantation, and in patients with cancer or AIDS. Whereas it is well known that gravity can be perceived by gravireceptors (statocyst-like organelles or gravisensitive ion channels in the cell membrane) in unicellular organisms such as Paramecium and Loxodes, where it strongly influences intracellular signal transduction and behaviour [5,6], the molecular mechanisms of gravisensitivity in mammalian cells are widely unknown. After the pioneering discovery of Cogoli et al. at the first Spacelab-Mission 20 years ago [7], it is known that proliferative response of lymphocytes after mitogenic stimulation is suppressed in microgravity [8]. In follow-up experiments in order to verify the result from Spacelab 1, it has been demonstrated clearly that factors other than microgravity can be excluded to be responsible for the depressed activation of lymphocytes. Whereas the phenomenon of reduced activation of T cells during microgravity is well described [9,10] and verified, the exact molecular mechanisms are not elucidated.Several investigations evidence alterations in signal transduction in lymphocytes. In lymphocytes, microgravity affected the protein kinase C [11,12] whereas delivery of first activation signal, patching and capping of conA-binding membrane proteins occurred normally in spaceflight [13]. These findings suggest the existence of gravisensitive cellular targets upstream from PKC and downstream from the TCR/CD3, where the lipid-raft-associated membrane-proximal signalosome comple
Signal transduction pathways in liver and the influence of hepatitis C virus infection on their activities  [cached]
Magdalena M Dabrowska, Anatol Panasiuk, Robert Flisiak
World Journal of Gastroenterology , 2009,
Abstract: In liver, the most intensively studied transmembrane and intracellular signal transduction pathways are the Janus kinase signal transduction pathway, the mitogen-activated protein kinases signal transduction pathway, the transforming growth factor β signal transduction pathway, the tumor necrosis factor α signal transduction pathway and the recently discovered sphingolipid signal transduction pathway. All of them are activated by many different cytokines and growth factors. They regulate specific cell mechanisms such as hepatocytes proliferation, growth, differentiation, adhesion, apoptosis, and synthesis and degradation of the extracellular matrix. The replication cycle of hepatitis C virus (HCV) is intracellular and requires signal transduction to the nucleus to regulate transcription of its genes. Moreover, HCV itself, by its structural and non-structural proteins, could influence the activity of the second signal messengers. Thus, the inhibition of the transmembrane and intracellular signal transduction pathways could be a new therapeutic target in chronic hepatitis C treatment.
Quantum walks and signal transduction pathways  [PDF]
Valentina Agoni
Physics , 2012,
Abstract: Signal transduction pathways recover a crucial role in cellular processes: they represent a connection between environmental conditions and cellular reactions. There are many pathways and they all are related to create a network. But how can every protein find the right way more fast than possible? How can it find the right down-streaming kinase in the cellular sea and not another very similar kinase? Every signal transduction pathway can be seen as two distincted processes: the signal must reach every kinase and then it must travel through the enzyme until its active site: quantum walks could be the answer to both the questions.
Context-dependent transcriptional regulations between signal transduction pathways
Sohyun Hwang, Sangwoo Kim, Heesung Shin, Doheon Lee
BMC Bioinformatics , 2011, DOI: 10.1186/1471-2105-12-19
Abstract: Applied to dendritic cells treated with lipopolysaccharide, our analysis well depicted how dendritic cells respond to the treatment through transcriptional regulations between signal transduction pathways in dendritic cell maturation and T cell activation.Our new approach helps to understand the underlying biological phenomenon of expression data (e.g. complex diseases such as cancer) by providing a graphical network which shows transcriptional regulations between signal transduction pathways. The software programs are available upon request.Signal transduction is the primary process by which cells coordinate their metabolism, proliferation, and cellular communication according to environmental signals such as hormones, nutrients, and other chemical stimuli. Cells sense environmental signals by receptor proteins which convert the signals into various responses through signal transduction that are dependent on cellular contexts such as signals, receptor proteins that cells possess, and intracellular machinery by which cells integrate and interpret the signals [1]. For example, the JAK-STAT signal transduction pathway, which provides one of the most direct routes from cell-surface receptors to a nucleus, is activated by more than 30 cytokines of soluble mediators in cell communication. The cellular responses are different according to their cytokines even though they are stimulated by the same JAK-STAT signal transduction pathway [1].As well as for various responses stimulated by signal transduction pathways or signaling pathways, recent articles have presented abundant evidence for inter-pathway cross-communication according to cellular contexts [2-4]. Cytokine signaling which is critical in immune system regulates functions of other signaling pathways either by transcription-mediated consequences of cytokine signaling or by transcription-independent mechanisms [2]. As an example of transcription-mediated mechanisms, interferon gamma activates signal transduction pat
BowTieBuilder: modeling signal transduction pathways
Jochen Supper, Lucía Spangenberg, Hannes Planatscher, Andreas Dr?ger, Adrian Schr?der, Andreas Zell
BMC Systems Biology , 2009, DOI: 10.1186/1752-0509-3-67
Abstract: Here, we present BowTieBuilder for inferring signal transduction pathways from multiple source and target proteins. Given protein-protein interaction (PPI) data signaling pathways are assembled without knowledge of the intermediate signaling proteins while maximizing the overall probability of the pathway. To assess the inference quality, BowTieBuilder and three alternative heuristics are applied to several pathways, and the resulting pathways are compared to reference pathways taken from KEGG. In addition, BowTieBuilder is used to infer a signaling pathway of the innate immune response in humans and a signaling pathway that potentially regulates an underlying gene regulatory network.We show that BowTieBuilder, given multiple source and/or target proteins, infers pathways with satisfactory recall and precision rates and detects the core proteins of each pathway.Most signal transduction events are initialized by cell-surface proteins that respond to specific environmental stimuli. When activated these proteins emanate a signaling cascade which involves a series of (de)-phosphorylation events. In many cases such signaling events transduce the signal to transcription factors (TFs), which in turn regulate the expression level of downstream genes. Understanding this cellular processing of information, from the source proteins (e.g., cell-surface proteins) to the target proteins (e.g., TFs), is important when generating comprehensive models of regulatory networks. For several biological processes the signaling pathway has been derived experimentally [1,2]. However, a large number of complex signaling pathways are yet to be discovered. To unravel these, computational inference methods are a valuable tool.The basis for the computational inference of novel signaling pathways are protein-protein interaction (PPI) datasets. These datasets are derived from biological studies on individual PPIs, but recently also by large-scale genomic, proteomic, and bioinformatic analyses. The
Application of Petri net based analysis techniques to signal transduction pathways
Andrea Sackmann, Monika Heiner, Ina Koch
BMC Bioinformatics , 2006, DOI: 10.1186/1471-2105-7-482
Abstract: We apply Petri net theory to model and analyse signal transduction pathways first qualitatively before continuing with quantitative analyses. This paper demonstrates how to build systematically a discrete model, which reflects provably the qualitative biological behaviour without any knowledge of kinetic parameters. The mating pheromone response pathway in Saccharomyces cerevisiae serves as case study.We propose an approach for model validation of signal transduction pathways based on the network structure only. For this purpose, we introduce the new notion of feasible t-invariants, which represent minimal self-contained subnets being active under a given input situation. Each of these subnets stands for a signal flow in the system. We define maximal common transition sets (MCT-sets), which can be used for t-invariant examination and net decomposition into smallest biologically meaningful functional units.The paper demonstrates how Petri net analysis techniques can promote a deeper understanding of signal transduction pathways. The new concepts of feasible t-invariants and MCT-sets have been proven to be useful for model validation and the interpretation of the biological system behaviour. Whereas MCT-sets provide a decomposition of the net into disjunctive subnets, feasible t-invariants describe subnets, which generally overlap. This work contributes to qualitative modelling and to the analysis of large biological networks by their fully automatic decomposition into biologically meaningful modules.Signal transduction pathways are of special interest in biological and medical sciences. Many diseases are related to disturbances in signalling pathways. For example protein-tyrosine kinases (PTKs) are important regulators of intracellular signal transduction pathways, mediating development and multicellular communication in metazoans. Their activity is tightly controlled and regulated, but perturbation of the normal autoinhibitory constraints on kinase activity can resu
Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways  [cached]
Mary Louisa Holton,Weiguang Wang,Michael Emerson,Ludwig Neyses
World Journal of Biological Chemistry , 2010,
Abstract: Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular free calcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulin-dependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.
Research Progress of Environmental Factors and Signal Transduction Pathways of Dimorphism in Fungi

LIU Juan,WU Yao,MA Ai-Min,CHEN Li-Guo,
刘 娟
,吴 尧,马爱民,陈立国

微生物学通报 , 2008,
Abstract: Dimorphism is the capacity displayed by different fungi to grow in the form of yeast or mycelium, depending on the environmental conditions. It has long been believed that phase transition between yeast and mycelium is obligatory for pathogenicity in some dimorphic fungi, so dimorphism of fungi attracts a great deal of attention in recent years. Dimorphic transition is regulated by a variety of extracellular factors including physical factors, chemical factors and nutritional factors, and it is also regulated by intracellular signal transduction pathways such as cAMP-PKA, MAPK and Rim101. This review focuses on recent research progress on environmental factors and signal transduction pathways that affect dimorphism in fungi.
Identification of photoperception and light signal transduction pathways in citrus
Quecini, Vera;
Genetics and Molecular Biology , 2007, DOI: 10.1590/S1415-47572007000500007
Abstract: studies employing model species have elucidated several aspects of photoperception and light signal transduction that control plant development. however, the information available for economically important crops is scarce. citrus genome databases of expressed sequence tags (est) were investigated in order to identify genes coding for functionally characterized proteins responsible for light-regulated developmental control in model plants. approximately 176,200 est sequences from 53 libraries were queried and all bona fide and putative photoreceptor gene families were found in citrus species. we have identified 53 orthologs for several families of transcriptional regulators and cytoplasmic proteins mediating photoreceptor-induced responses although some important arabidopsis phytochrome- and cryptochrome-signaling components are absent from citrus sequence databases. the main gene families responsible for phototropin-mediated signal transduction were present in citrus transcriptome, including general regulatory factors (14-3-3 proteins), scaffolding elements and auxin-responsive transcription factors and transporters. a working model of light perception, signal transduction and response-eliciting in citrus is proposed based on the identified key components. these results demonstrate the power of comparative genomics between model systems and economically important crop species to elucidate several aspects of plant physiology and metabolism.
Enzyme Localization Can Drastically Affect Signal Amplification in Signal Transduction Pathways  [PDF]
Siebe B van Albada,Pieter Rein ten Wolde
PLOS Computational Biology , 2007, DOI: 10.1371/journal.pcbi.0030195
Abstract: Push–pull networks are ubiquitous in signal transduction pathways in both prokaryotic and eukaryotic cells. They allow cells to strongly amplify signals via the mechanism of zero-order ultrasensitivity. In a push–pull network, two antagonistic enzymes control the activity of a protein by covalent modification. These enzymes are often uniformly distributed in the cytoplasm. They can, however, also be colocalized in space; for instance, near the pole of the cell. Moreover, it is increasingly recognized that these enzymes can also be spatially separated, leading to gradients of the active form of the messenger protein. Here, we investigate the consequences of the spatial distributions of the enzymes for the amplification properties of push–pull networks. Our calculations reveal that enzyme localization by itself can have a dramatic effect on the gain. The gain is maximized when the two enzymes are either uniformly distributed or colocalized in one region in the cell. Depending on the diffusion constants, however, the sharpness of the response can be strongly reduced when the enzymes are spatially separated. We discuss how our predictions could be tested experimentally.
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