Angiogenesis, the formation of new blood vessels from pre-existing ones, occurs during development, wound healing and cancer and involves stages that orchestrate a network of cooperative interactions. Peptide growth factors and extracellular matrix (ECM) components are two major groups of angiogenesis mediators. Among the different ECM proteins, collagens have been well-associated with in vivo angiogenesis. Using human umbilical vein endothelial cells (HUVEC) grown in 3-D collagen gels we show that: (1) HUVEC do not survive well in 3-D collagen gels due to rapid induction of apoptosis. (2) VEGF, a potent in vivo angiogenic factor, fails to induce tube formation. (3) PMA was effective in inducing tube formation and survival in HUVEC dispersed in 3-D collagen gels, activating MAP kinase, phosphoinositide 3-OH kinase (PI-3-kinase) and Akt/PKB (protein kinase B) pathways. (4) VEGF was effective in preventing PMA-induced tube-like structure regression after PMA-withdrawal by (5) activating the ...

en] Biological systems and, in particular, cellular signal transduction pathways are characterised by their high complexity. Mathematical models describing these processes might be of great help to gain qualitative and, most importantly, quantitative knowledge about such complex systems. However, a detailed mathematical description of these systems leads to nearly unmanageably large models, especially when combining models of different signalling pathways to study cross-talk phenomena. Therefore, simplification of models becomes very important. Different methods are available for model reduction of biological models. Importantly, most of the common model reduction methods cannot be applied to cellular signal transduction pathways. Using as an example the epidermal growth factor (EGF) signalling pathway, we discuss how quantitative methods like system analysis and simulation studies can help to suitably reduce models and additionally give new insights into the signal transmission and processing ...

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein ...

Growth factor signaling in neurons controls the expansion of synaptic arbors in response to activity and external stimuli, leading to long-lasting changes in synapse strength and connectivity that underlie learning and memory. Receptor complexes regulating growth factor signal transduction are internalized via endocytosis and directed to specific subcellular membrane compartments from which they exhibit distinct signaling properties, caused by compartment-specific posttranslational modifications and degradative events, or interactions with local binding partners (Sadowski et al., 2009). Therefore, defining the mechanisms by which the rate and direction of the flow of endosomal protein traffic are controlled is critical to determining how neuronal signal transduction pathways are tuned up and down after activation. A host of protein factors control membrane traffic through the interconnected tubules and vesicles of the endosomal system, and sorting occurs by isolation of cargo in membrane domains ...

Title: The FRK / RAK-SHB Signaling Cascade: A Versatile Signal- Transduction Pathway that Regulates Cell Survival, Differentiation and Proliferation. VOLUME: 3 ISSUE: 4. Author(s):Cecilia Anneren, Cecilia K. Lindholm, Vitezslav Kriz and Michael Welsh. Affiliation:Department of Medical Cell Biology, Husargatan 3, 75237, Uppsala, Sweden.. Keywords:signal-transduction pathway, proliferation, src homology 2, sh2 domain adapter protein. Abstract: Recent experiments have unravelled novel signal transduction pathways that involve the SRC homology 2 (SH2) domain adapter protein SHB. SHB is ubiquitously expressed and contains proline rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites and an SH2 domain and serves a role in generating signaling complexes in response to tyrosine kinase activation. SHB mediates certain responses in platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell ...

TY - JOUR. T1 - Sirt1 Regulates Microtubule Dynamics Through Negative Regulation of Plk1 in Mitosis. AU - Kim, Jin Ju. AU - Gil, Na Yeon. AU - Zhang, Xiang Hua. AU - Chun, Kwang Hoon. AU - Fang, Guowei. AU - Kim, Joon. AU - Cho, Hyeseong. AU - Jang, Chang Young. AU - Cha, Hyuk Jin. PY - 2015/9/1. Y1 - 2015/9/1. N2 - Although loss of Sirt1 leads to chromosome aneuploidy, which accounts for higher tumor susceptibility, the molecular mechanisms remain unclear. Herein, we demonstrate that Sirt1 directly regulates Plk1, of which activity is critical for mitotic progression and spindle dynamics. Depletion or inhibition of Sirt1 significantly perturbs the formation of the mitotic spindle, leading to defective chromosome segregation. Elevated depolymerization of the mitotic spindle following loss of Sirt1 was associated with the deregulation of Plk1 activity. Thus, we conclude that Sirt1 may contribute to a mitotic regulator that controls spindle dynamics through Plk1 activity, resulting in fine-tuning ...

The regulatory signaling pathways crucial during embryonic development seem to play key roles in adult tissues homeostasis and are often deregulated in pathological conditions. The Wnt pathway plays a pivotal role in orchestrating cell fate decisions during embryonic development, organogenesis, and adult tissues homeostasis of endoderm-derived tissues. The canonical Wnt ... read more signaling is required at different stages of embryonic development, regulating gut patterning and organogenesis, and is instrumental for the maintenance of the intestine epithelium homeostasis in adults. Tumorigenesis arises as a disruption of the homeostatic state of a tissue. Initiation of colorectal tumorigenesis is principally associated with mutations in the APC gene, a central component of the canonical Wnt pathway. Studies of early embryonic events and molecular mechanisms regulating tissue morphogenesis and organogenesis are challenging in higher vertebrates. Due to the large clutch size, ex utero ...

Structural approaches are becoming increasingly important for our understanding of cell biology, as the functioning of gene products needs to be analysed in the context of the complex organisation of cells and cannot be understood by studying proteins in isolation alone. This holds particularly true for components of cellular signal transduction pathways. It is now clear that subcellular compartmentalisation and spatiotemporal turnover (i.e. distribution within the cellular structures) of signal transduction components are playing a critical role in the response of cells to extrinsic stimulation. Methods of biochemistry and molecular genetics are widely employed to analyse protein interactions and dissect signalling pathways - however, these approaches yield little information with regard to relevant structural aspects.. In recent years, the concept of differential cellular signalling through recruitment of signal transduction molecules into specialised plasma membrane microdomains, so-called ...

Signal Transduction Pathways in Breast Cancer: The Important Role of PI3K/Akt/mTOR Miguel A. Ortega , 1 , 2 , 3 Oscar Fraile-Martínez , 1 Ángel Asúnsolo , 2 , 4 Julia Buján , 1 , 2 Natalio García-Honduvilla , 1 , 2 and Santiago Coca 1 , 2 Discovery of the Hippo signal transduction network. On several proteins, O-GlcNAc and O-phosphate alternatively occupy the same or adjacent sites, leading to the hypothesis that one function of this saccharide is to transiently block phosphorylation. Enormous advances have been made over the last 10 years in unravelling cytokine signal transduction. The functioning of a signal transduction pathway is based on extra-cellular signaling that in turn creates a response that causes other subsequent responses, hence creating a chain reaction, or cascade. 2003 ; Grefen et al. (+1) 510 642 2293; Fax (+1) 510 643 6334. Aim: Urokinase is an important and critical enzyme of the Pulmonary renal cascade. Signal transduction in the immune system, the coupling between ...

Title:An Integrated and Disease-Oriented Growth Factor-Regulated Signal Transduction Network. VOLUME: 13 ISSUE: 1. Author(s):A. Erol. Affiliation:Mimar Sinan Mahallesi, Muammer Aksoy Caddesi, Elmassokak 4, Silivri-Istanbul, Turkey.. Keywords:Akt, β-catenin, Erk, E2F1, DAPK, GSK3, mTORC1, mTORC2, Pin1, Wnt. Abstract:The importance of Akt, Erk, and their downstream effectors-mediated signaling is indisputable for the proliferation of cell. Growth factor-induced activation of Akt and Erk pathways interacts with each other to regulate proliferation. However, an instructive model, wiring the crucial signaling nodes working in cellular growth and division, is still absent or controversial. Although growth factor-mediated mTORC1 regulation is defined considerably, debates still exist formTORC2. TSC1-TSC2 complex integrates both nutrient and mitogenic signals coming from growth factor receptors. Growth factor-induced PI3K/Akt- and Ras/Erk-mediated TSC2 inhibition is well defined. However, the ...

Application of Petri net based analysis techniques to signal transduction pathways - Background: Signal transduction pathways are usually modelled using classical quantitative methods, which are based on ordinary differential equations (ODEs). However, some difficulties are inherent in this approach. On the one hand, the kinetic parameters involved are often unknown and have to be estimated. With increasing size and complexity of signal transduction pathways, the estimation of missing kinetic data is not possible. On the other hand, ODEs based models do not support any explicit insights into possible (signal-) flows within the network. Moreover, a huge amount of qualitative data is available due to high-throughput techniques. In order to get information on the systems behaviour, qualitative analysis techniques have been developed. Applications of the known qualitative analysis methods concern mainly metabolic networks. Petri net theory provides a variety of established analysis techniques, which are

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. 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. We show that our technique accurately reconstructs MAP Kinase signaling networks in Saccharomyces cerevisiae.

1680 Cell density is a potent regulator of the cell cycle during exponential growth and thus affects gene expression. Many recent studies have characterized cell-density as a controlling factor for cell-cell interactions and the binding of surface-associated adhesion molecules to the cytoskeleton. We examined the impact of cell density on two distinct signal transduction pathways, Protein kinase B (Akt) and Mitogen-activated protein kinases (MAPK). These pathways regulate cell proliferation, differentiation, and apoptosis, and exhibit cross-talk. Downstream, the MAPK and Akt pathways regulate p70S6kinase (p70S6K) and its substrate S6 ribosomal protein (S6RP). Whereas levels of phospho-S6RP are known to be regulated by phosphorylated-Akt, our findings suggest that in Jurkat cells this is dependent upon the cell density. We show that maximum phosphorylation of S6RP(S235/S236 and S240/244) is observed at lower cell densities (0.5x106 cells/mL). In contrast, levels of phosphorylated Akt increase ...

Clone REA812 recognizes the human CD163 antigen, a single-chain transmembrane protein also known as hemoglobin scavenger receptor or M130. It is expressed by mature tissue macrophages and peripheral blood monocytes. The expression of CD163 is up-regulated in vitro and in vivo by anti-inflammatory mediators such as interleukin 10 (IL-10) and (gluco)corticosteroid and is shed to blood upon inflammatory activation of macrophages. CD163 functions as a high affinity scavenger receptor for the complex of haemoglobin and haptoglobin. Depending on the ligand, crosslinking of CD163 initiates signal transduction leading to the production of proinflammatory cytokines Il-1ß, IL-6, and GM-CSF or the anti-inflammatory cytokine IL-10. Additional information: Clone REA812 displays negligible binding to Fc receptors. - Latvija

Cytokine signal transduction is essential for normal immune function and controls the quality of responses to a wide variety of microbial infections. Innate and adaptive host responses to virus infections are regulated by autocrine and paracrine cytokine signaling systems. For most cytokines, receptor binding triggers an intracellular signaling cascade involving one or more signal transducer and activator of transcription (STAT) proteins. Diverse cytokine and growth factor signaling pathways produce active STAT transcription factors that specify mRNA induction profiles (26). For example, the alpha and beta interferon (IFN-α/β) family is of primary importance for both innate and adaptive antiviral immunity (reviewed in references 1, 49, and 53). In the innate antiviral system, IFN-α/β initiates a receptor-mediated signaling system that produces an activated STAT1-STAT2-IRF9 heterotrimeric transcription complex known as ISGF3 (27). The ISGF3 complex translocates to the nucleus, where it can ...

Extracellular signals transduced by both RTKs and GPCRs converge upon the activation of a family of PI3Ks. Activation of these lipid kinases by GPCRs is thought to be dependent on the direct binding of Gβγ subunits and Ras to PI3Ks [88]. PI3K activation initiates a phosphorylation cascade leading to the activation of Akt (also termed protein kinase B) and its downstream kinases phosphoinositide-dependant kinase 1 (PDK1), glycogen synthase kinase 3 (GSK3), p70 ribosomal protein S6 kinase (p70S6K), mammalian target of rapamycin (mTOR) and others [89]. In addition, we have already seen how GPCRs can activate PI3K pathways via RTK or integrin transactivation [41,42,66]. Following direct or indirect GPCR-induced PI3K activation, cell cycle progression is regulated by the effect of PI3K-activated kinases on the expression and stability of cell cycle proteins, or by the modulation of the activity of other signal transduction pathways. For example, somatostatin SST2 receptors expressed in Chinese ...

Post-Doctoral Position,br, Arabidopsis Signal Transduction,br, A post-doctoral position is available immediately in the laboratory of Mannie Liscum at the University of Missouri-Columbia.  This project deals with the reverse genetic analyses of the ,i,NPH3,/i,/,i,RPT2,/i, gene family in Arabidopsis.  This large family of genes (>15 members) encode novel proteins, however both NPH3 and RPT2 have been shown genetically to be required for early signal transduction during response to phototropic stimuli.  We hypothesize that this novel family of proteins function as molecular scaffolds to mediate the assembly/stability of signal transduction components in a variety of signal-response systems (i.e., not limited to phototropism).  A variety of approaches will be used address the biological roles of members of this family, including isolation of knock-out mutants via T-DNA and transposon mutagenesis, generation of mutants through anti-sense construction, and transgenic ...

The maternal D-raf serine/threonine kinase acts downstream of Torso (Tor) for specification of cell fates at the embryonic termini. D-raf activity is also required in other signal transduction pathways and consistent with its pleiotropic role, we find accumulation of a 90-kD D-raf protein throughout embryonic development. We also characterize the accumulation of maternal D-raf proteins in 0-2-hr embryos derived from females with germ cells lacking D-raf activity. Accumulation of a 90-kD or truncated mutant D-raf protein is observed for some of these embryos, while others lack the maternal D-raf protein. Then, to determine whether rescue of the Tor pathway is influenced by pools of nonfunctional maternal D-raf, wild-type D-raf mRNA was injected into embryos that inherit maternal stores of inactive 90-kD or truncated D-raf protein. For embryos lacking the maternal D-raf protein, a high level of terminal rescue is obtained. In contrast, rescue is reduced or not observed for embryos that accumulate ...

DNA double strand breaks are the pivotal cellular damage induced by ionizing radiation. A plethora of molecular and cellular processes are activated as part of the cellular stress response that result in cell cycle arrest and induction of the DNA-repair machinery to restore the damage of DNA or to activate a cell death program. However ionizing radiation also initiates signal transduction cascades that are generated at cellular sites distant from and independent of DNA-damage. These signaling processes are similar to hormone activated growth factor receptor controlled signal transduction cascades and represent interesting targets for anticancer treatment modalities combining ionizing radiation with molecular defined pharmacological compounds. Activation of these signal transduction cascades upon irradiation or upregulation of growth factor mediated pathways due to oncogene-transformation often contribute to an acquired or inherent treatment resistance in malignant cells. Therefore ...

Biological signal transduction networks are commonly viewed as circuits that pass along information-in the process amplifying signals, enhancing sensitivity, or performing other signal-processing tasks-to transcriptional and other components. Here, we report on a reverse-causality phenomenon, which we call load-induced modulation. Through a combination of analytical and experimental tools, we discovered that signaling was modulated, in a surprising way, by downstream targets that receive the signal and, in doing so, apply what in physics is called a load. Specifically, we found that non-intuitive changes in response dynamics occurred for a covalent modification cycle when load was present. Loading altered the response time of a system, depending on whether the activity of one of the enzymes was maximal and the other was operating at its minimal rate or whether both enzymes were operating at submaximal rates. These two conditions, which we call limit regime and intermediate regime, were ...

Background: Akt is a critical molecule in several signal transduction pathways involved in vascular responses. Membrane type 1-matrix metalloproteinase (MT1-MMP), a membrane-anchored MMP, functions as a signaling molecule in addition to a proteolytic enzyme.. Hypothesis: Akt cooperates with MT1-MMP in tumor necrosis factor (TNF)-alpha-induced signaling pathways of vascular responses including endothelial dysfunction and haemostasis.. Methods and Results: TNF-alpha (10 ng/mL) induced a transient increase in Akt phosphorylation within 15 minutes, followed by the profound decrease of Akt phosphorylation and the increase in MT1-MMP activity within 60 minutes, in cultured human aortic endothelial cells (ECs). To demonstrate the role of MT1-MMP for Akt signaling pathway in TNF-alpha-stimulated ECs, we used siRNA to knockdown MT1-MMP protein in ECs. Silencing of MT1-MMP reversed TNF-alpha-triggered transient upregulation of Akt phosohorylation within 15 minutes and the downregulation within 60 minutes, ...

As the key neuron-to-neuron interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. However, the signal transduction mechanisms by which stress mediates its lasting effects on synapse transmission and on memory are not fully understood. A key component of the stress response is the increased secretion of adrenal steroids. Adrenal steroids (e.g., cortisol) bind to genomic mineralocorticoid and glucocorticoid receptors (gMRs and gGRs) in the cytosol. In addition, they may act through membrane receptors (mMRs and mGRs), and signal transduction through these receptors may allow for rapid modulation of synaptic transmission as well as modulation of membrane ion currents. mMRs increase synaptic and neuronal excitability; mechanisms include the facilitation of glutamate release through extracellular signal-regulated kinase signal transduction. In contrast, mGRs decrease synaptic and neuronal excitability by reducing calcium currents through ...

FIG. 3. Alignment of the H-box sequence containing the phosphoaccepting histidine. Subalignments of the H-box region (58) from the sequence alignment used for Fig. 2 are shown. For each group, the consensus sequences for N. crassa (Nc), G. moniliformis (Gm), B. fuckeliana (Bf), and C. heterostrophus (Ch) are shown in bold at the top. (A) Conserved HK groups. Lowercase letters indicate amino acid residues that are not absolutely conserved among orthologs in the four euascomycetes considered here. Sequences from other ascomycetes (underlined) or paralogs (italicized) are represented by dashes for consensus (conserved) residues or the appropriate amino acid. (B) Divergent HK groups. All sequences are shown, even when two or more paralogs have identical H-box sequences. Absolutely conserved residues are shaded black, and residues conserved in at least 50% of all sequences are shaded gray. Asterisks indicate positions of conserved histidine residues. ...

Since the discovery of the lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) by Sawamura and colleagues in 1997, this multi-ligand receptor has been implicated in atherosclerosis and diabetes. Oxidised LDL binding and trafficking via LOX-1 cause the activation of downstream signal transduction that cause pro-athrogenic changes such as endothelial dysfunction, apoptosis and foam cell formation. However, the molecular mechanisms have not be been fully explained. In this study, tetracycline- inducible cell lines expressing LOX-1 wild-type and trafficking-defective LOX-1-D5A were developed. The findings show different trafficking properties between LOX-1-WT and LOX-1-D5A in response to oxidised LDL. Due to these differences, LOX-1-WT and LOX-1-D5A in response to oxidised LDL exhibited differential downstream signal transduction. Moreover, 24 hour stimulation of oxidised LDL via LOX-1-WT caused decreased endothelial cell permeability; however, the underlying mechanism is not clear. The ...

Cerebral cortical development requires orderly transitions between neurogenesis and differentiation. Neurogenesis also results in overproduction of neurons that are selectively targeted for apoptosis. In these experiments, we conditionally immortalized (Almazan and McKay, 1992; Yanai and Obinata, 1994; Taher et al., 1995; Eves et al., 1996) neural precursors from embryonic rat cerebral cortex, to contrast estrogen and neurotrophin regulation of p53-dependent cortical differentiation and death.. The large T antigen promotes mammalian cell cycle by inhibiting checkpoint transcription factors like p53 (for review, see Levine, 1997). Consequently, the Ts/U19 large T antigen mutation permits synchronization of differentiation, by conditionally regulating p53-dependent mechanisms. At the nonpermissive temperature (39°C), large T antigen expression ceases and substantial cell death occurs, that is partly caused by apoptosis. At this temperature, we also observed induction of pp53 and p53-dependent ...

For example, in frogs, cyclin dependent protein kinase 2 (CDK2) binds to cyclin B to form an active kinase which phosphorylates a prereplication complex initiating S phase and mitosis. Cyclin B, a 45Kd protein, accumulates to high levels just before S phase. Its concentration drops sharply at the end of mitosis. The kinase, a 34 Kd protein, is encoded by the CDC2 gene (for cell division cycle gene). A homologous gene exists in humans - the CDK2 gene (cyclin dependent kinase 2) - and controls entry in S phase. These kinases can be considered heterodimers with a kinase catalytic subunit and a cyclin regulatory subunit. In animal cells, there are at least ten different cyclins (A, B, .....) and at least eight different cyclin-dependent kinases (CDK1-8). Another Look at Neurotransmission and Ion Channels. You may have noticed above that some signaling molecules, whose effects are regulated by kinases (b-adrenergic and some olfactory signals by PKA and acetylcholine by PKC for example), are ...

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Nitric oxide is a ubiquitous signaling molecule with both physiological and pathological functions in biological systems. Formed by the enzymatic conversion of arginine to citrulline, NO, has known roles in circulatory, immune and nervous tissues. In the nervous system nitric oxide has been implicated in long-term potentiation, neurotransmitter release, channel function, neuronal protection and neuronal degeneration. Much of our work has focused on yet another role for nitric oxide in cells, namely, neuronal differentiation. During development, neuronal differentiation is closely coupled with cessation of proliferation. We use nerve growth factor (NGF)-induced differentiation of PC12 pheochromocytoma cells as a model and find a novel signal transduction pathway that blocks cell proliferation. Treatment of PC12 cells with NGF leads to induction of nitric oxide synthase (NOS). The resulting nitric oxide (NO) acts as a second messenger, activating the p21(WAF1) promoter and inducing expression of p21(WAF1)

Genomes and Genes, Species, Research Topics, Scientific Experts, Publications about Experts and Doctors on signal transduction in Holland, Michigan, United States

Species, Publications, Research Topics, Genomes and Genes, Locale, Scientific Experts about Experts and Doctors on signal transduction in Shanghai, Shanghai Shi, China

Clone REA508 recognizes the human ErbB-3 antigen, a single-pass type I membrane protein, which is also known as tyrosine kinase-type cell surface receptor HER3. ErbB-3 is a receptor tyrosine kinase and a member of the epidermal growth factor receptor family (EGFR). It is unique among the ErbB family members in that it is has been shown to have weak or no tyrosine kinase activity. After dimerization with other members of the EGFR family several signal transduction cascades can be activated, including phosphoinosite 3-kinase (PI3-K)/Akt and extracellular signal-regulated kinase (ERK1/2). ErbB-3 is widely expressed in normal tissues including cells of the gastrointestinal, reproductive, respiratory and urinary tracts, as well as the skin, endocrine, and nervous system. It is expressed at elevated levels in a range of human malignancies. Additional information: Clone REA508 displays negligible binding to Fc receptors. - Principat dAndorra

Postdoc position - signal transduction & transcription Applications are invited for postdoctoral positions in a newly established research group at the Ludwig Institute for Cancer Research (LICR) in Uppsala, Sweden. The successful candidates will study the transcriptional regulation of metabolic pathways and the transcriptional mechanisms of growth factor signal transduction (Ericsson et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 945-950; Ericsson et al. (1996) J. Biol. Chem., 271, 24359-24367; Ericsson and Edwards. (1998) J. Biol. Chem., in press; Heldin et al. (1997) Nature, 390, 465-471; Dennler et al. (1998) EMBO J., 17, 3091-3100). The aim is to identify the downstream targets (i.e. transcription factors, coactivators and corepressors) of these signaling pathways and to determine how these molecules regulate gene expression. We are also interested in how abnormal regulation of these processes is related to the development of human disease. We are seeking highly motivated scientists ...

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear ...

A. Cellular Signal Transduction: Using cells KDd, KOd or mutated for AD/AR-PKD or cystic kidney syndromic genes [Identification of potential signaling defects]. 1. Measure steady state activities of cellular signal transduction pathways such as MAP kinase, Hippo, canonical Wnt and Sonic Hedgehog (previously implicated in AD- and ARPKD and ciliopathies) [Immunofluorescence and quantitative immunoblotting and mass. 2. Measure the steady-state activity and agonist-induced transcriptional response of jun, yap/taz, tcf and gli transcription factors. [qPCR]. 3. Investigate downstream activation of CREB and NFAT transcription factors that are downstream of second messenger signaling of cAMP and Ca2+, respectively [qPCR, Immunofluorescence and quantitative immunoblotting and mass spectrometry]. B. Cellular and Ciliary Dynamics: Using fluorescent protein-based localization and activity reporters [Consultation for detailed temporal measurements of signaling]. 1. Measure Hh (Smo translocation, Gli ...

The basal ganglia is a critical regulator of a myriad of processes in the brain including motor control and behavior. This system is divided into several nuclei...

The Gene Ontology (GO) project is a collaborative effort to address the need for consistent descriptions of gene products across databases. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated gene data at MGI are provided in Term Detail reports.

This enzyme hydrolyses 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. The enzyme also shows activity toward (PtdIns(1,3,4,5)P4) [5]. The enzyme is involved in several signal transduction pathways in the immune system leading to an adverse range of effects ...

beyond the classical view of a synapse to a more sophisticated, view, in which considers post-receptor, intracellular messenger pathways.. This means that, despite the initial actions of a drug or stress on the activity of a neurotransmitter or receptor system, the many actions of drugs and stress on brain function are achieved ultimately through the complex network of intracellular messenger pathways that mediate physiological responses to neurotransmitter-receptor interactions. These intracellular pathways consist of G proteins, second messenger systems, protein kinases, and protein phosphatases, among many others. Repeated exposure to drugs and stress would be expected to produce molecular and cellular adaptations as a result of repeated perturbation of these intracellular pathways. We believe that these adaptations are ultimately responsible for many features of addiction and depression. ...

Cellular responses are triggered by proteins, drugs, or pathogens binding to specific receptors. Receptor mediated signaling is a cascade of enzymatic reactions that amplifies the signal. The agonists and antagonists modulating receptor functionality are essential tools for research and medical practice. read more. ...

Currently, there are no PET radiotracers or MRI techniques that allow for noninvasive assessment of hypoxia-induced molecular-genetic and signaling processes in cells at transcriptional and post-transcriptional levels. Therefore, to study the temporal dynamics and spatial heterogeneity of hypoxia development and HIF-1-mediated transcriptional activation of hypoxia-inducible genes, we developed a novel HIF-1-specific reporter system that allows for noninvasive in vivo PET imaging in living mice. The Red2XPRT beacon gene (16) facilitates the imaging of transduced cell (tissue) localization, whereas the TKGFP sensor gene (19) allows for imaging of HIF-1 transcriptional activity. Furthermore, both reporter genes encode PET reporter enzymes (XPRT or HSV1-TK), which metabolically entrap specific radiolabeled probes (xanthine or FEAU) in transduced cells (16 , 19) . These enzymes are fused with fluorescent proteins (DsRed or eGFP) that allow for fluorescence microscopic visualization of expression ...

Compare T cell, immune regulator 1, ATPase, H transporting, lysosomal V0 protein A3 T cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 protein A3 ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, reviews, and more.

The Raf-1 protein, encoded by the c-raf-1 gene, is a 75 kDa serine-threonine kinase that functions as a key regulator of cell growth, proliferation, and survival (1) . Raf-1 is a critical component of multiple signal transduction pathways, integrating signals from cell membrane-bound growth factor receptors and apoptotic regulators (2) . Activated Raf-1 in turn interfaces with a many downstream targets controlling proliferation and survival, including activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinases MEK1 and MEK2, activation of the nuclear factor κB survival and proliferation pathway, and inhibition of the proapoptotic factor Bad (3) .. Deregulated Raf-1 activity has been implicated in oncogenic transformation (4 , 5) . Constitutive Raf-1 activation leads to morphological changes consistent with a malignant phenotype, to growth factor-independent proliferation, and to increased resistance to cytotoxic agents (6) . Raf-1 promotes full malignant ...

Lung cancer is the primary cause of cancer-related mortality worldwide and although improvements in treatment have been achieved over the last few years, long-term survival rates for lung cancer patients remain poor. Therefore, there is an imperative need for molecularly targeted agents that will achieve long-term disease control. Numerous downstream molecular pathways, such as EGF/RAS/RAF/MEK/ERK and PI3K/AKT/mTOR are identified as having a key role in the pathogenesis of various forms of human cancer, including lung cancer. PI3K/AKT/mTOR signal pathway is an important intracellular signal transduction pathway with a significant role in cell proliferation, growth, survival, vesicle trafficking, glucose transport, and cytoskeletal organization. Aberrations in many primary and secondary messenger molecules of this pathway, including mutations and amplifications, are accounted for tumor cell proliferation, inhibition of apoptosis, angiogenesis, metastasis and resistance to chemotherapy-radiotherapy. In

In cellular signal transduction, scaffold proteins provide binding sites to organize signaling proteins into supramolecular complexes and act as nodes in the signaling network. Furthermore, multivalent interactions between the scaffold and other signaling proteins contribute to the formation of protein microclusters. Such microclusters are prominent in early T cell signaling. Here, we explored the minimal structural requirement for a scaffold protein by coupling multiple copies of a proline-rich peptide corresponding to an interaction motif for the SH3 domain of the adaptor protein GADS to an N-(2-hydroxypropyl)methacrylamide polymer backbone. When added to GADS-containing cell lysates, these scaffolds (but not individual peptides) promoted the binding of GADS to peptide microarrays. This can be explained by the cross-linking of GADS into larger complexes. Furthermore, following import into Jurkat T cell leukemia cells, this synthetic scaffold enhanced the formation of microclusters of signaling ...

QIAGEN provides a broad range of assay technologies for signal transduction research, enabling analysis of gene expression and regulation, epigenetic modification, genotyping, and signal transduction pathway activation. Signal transduction transmits and amplifies signals of stimuli from extracellular sources to the nucleus. Signaling molecules include various hormones, growth factors, metabolites, cytokines, chemokines, neurotransmitters, extracellular matrix components, receptors, protein kinases, protein phosphatases, and DNA-binding proteins. The purpose of signal transduction is to regulate the cellular response to the molecular stimuli via changes in gene and protein expression. Solutions optimized for these research studies are organized into more focused research topics, shown below ...

Phosphorylation of specific tyrosine and threonine residues in the activation loop of this enzyme by EC 2.7.12.2 is necessary for enzyme activation. -!- Once activated, the enzyme phosphorylates target substrates on serine or threonine residues followed by a proline. -!- A distinguishing feature of all MAPKs is the conserved sequence Thr- Xaa-Tyr (TXY). -!- Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. -!- Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumor necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischemeic injury. -!- Formerly EC 2.7.1.37 ...

Multifunctional glycoprotein that acts as receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipidic nature such as oxidized low-density lipoprotein (oxLDL), anionic phospholipids, long-chain fatty acids and bacterial diacylated lipopeptides (PubMed:7685021). They are generally multivalent and can therefore engage multiple receptors simultaneously, the resulting formation of CD36 clusters initiates signal transduction and internalization of receptor-ligand complexes. The dependency on coreceptor signaling is strongly ligand specific. Cellular responses to these ligands are involved in angiogenesis, inflammatory response, fatty acid metabolism, taste and dietary fat processing in the intestine (Probable) (PubMed:19847289, PubMed:20037584, PubMed:23395392). Binds long-chain fatty acids and facilitates their transport into cells, thus participating in muscle lipid utilization, adipose energy storage, and gut

Signal transduction is any process by which a cell converts one kind of signal or stimulus into another. Processes referred to as signal transduction often involve a sequence of biochemical reactions inside the cell, which are carried out by enzymes and linked through second messengers. In many transduction processes, an increasing number of enzymes and other molecules become engaged in the events that proceed from the initial stimulus. Responses of cells to environmental signals, toxins and stressors have profound implications for diverse aspects of human health and disease including development, cystic fibrosis, diabetes, asthma, heart, autoimmune diseases and cancer. The delineation of the signal transduction pathways affected in these and other complex human diseases are likely to present new avenues for therapeutic intervention and understanding of human disease mechanisms ...

In this paper, we propose a stochastic simulation to model and analyze cellular signal transduction. The high number of objects in a simulation requires advanced visualization techniques: first to handle the large data sets, second to support the human perception in the crowded environment, and third to provide an interactive exploration tool. To adjust the state of the cell to an external signal, a specific set of signaling molecules transports the information to the nucleus deep inside the cell. There, key molecules regulate gene expression. In contrast to continuous ODE models we model all signaling molecules individually in a more realistic crowded and disordered environment. Beyond spatiotemporal concentration profiles our data describes the process on a mesoscopic, molecular level, allowing a detailed view of intracellular events. In our proposed schematic visualization individual molecules, their tracks, or reactions can be selected and brought into focus to highlight the signal ...

Dear Colleagues,. We would like to inform you that the registration and abstract submission for the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers is open till 31st of July and we are looking forward to your registration!. The symposium will be held September 13-15, 2017 in Kraków, Poland.. For more information please see: http://bbb.pan.olsztyn.pl/. The program covers all areas of blood-brain barriers research and reflects the latest developments in neurodegenerative diseases, membrane receptors and transporters, transcytosis regulators, epigenetic and transcriptional regulators, metabolic and nutrition regulation, in vivo and in vitro brain barriers models as well as the role of tight junctions and glycocalyx in blood brain barrier permeability. In addition, signaling pathways implicated in the development of neurological diseases and brain tumors are addressed.. We hope to meet you all in Kraków for this anniversary Blood-Brain Barriers event!. Best ...

Dear Colleagues,. We would like to inform you that the registration and abstract submission for the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers is open till 31st of July and we are looking forward to your registration!. The symposium will be held September 13-15, 2017 in Kraków, Poland.. For more information please see: http://bbb.pan.olsztyn.pl/. The program covers all areas of blood-brain barriers research and reflects the latest developments in neurodegenerative diseases, membrane receptors and transporters, transcytosis regulators, epigenetic and transcriptional regulators, metabolic and nutrition regulation, in vivo and in vitro brain barriers models as well as the role of tight junctions and glycocalyx in blood brain barrier permeability. In addition, signaling pathways implicated in the development of neurological diseases and brain tumors are addressed.. We hope to meet you all in Kraków for this anniversary Blood-Brain Barriers event!. Best ...

The organizing committee warmly invites you to the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers, which will be held September 13-15, 2017 in Kraków, Poland.. Kraków (English: Krakoof) is one of the oldest cities in Poland, dating back to the 7th century. Situated on the Vistula (Polish: Wisła) River, it was the capital of the Kingdom of Poland from 1038 to 1795. Kraków is one of the leading centers of Polish academic, cultural, and artistic life, and is the home of the second oldest university in Central Europe (namely, the Jagiellonian University), alma mater of Nicolaus Copernicus and the Nobel laureate Maria Skłodowska-Curie.. Krakóws historic center includes: the Old Town, with the largest medieval market square in Europe; Kazimierz, an old Jewish district; and the Wawel Castle. Kraków was named European Capital of Culture in 2000.. The symposium program covers all areas of blood-brain barriers research and reflects the latest developments in ...

Neuronal growth factors regulate the expression of voltage-activated sodium current in differentiating sympathetic neurons and PC12 cells. We show that, in PC12 cells, the NGF- and FGF-induced sodium current results from increased expression of two distinct sodium channel types. Sodium current results from the rapid induction of a novel sodium channel transcript, also found in peripheral neurons, and from the long term induction of brain type II/IIA mRNA. Expression of the type II/IIA sodium channel requires activation of the cyclic AMP-dependent protein kinase (A-kinase), whereas induction of the peripheral neuron type sodium channel occurs through an A-kinase-independent signal transduction pathway. These findings suggest that the two sodium channel types act in concert to ensure the generation of action potentials during neuronal differentiation. ...

The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1. These data demonstrate that the nucleus is one target of the p38 MAP kinase signal transduction pathway. ...

Raingeaud J., Whitmarsh A.J., Barrett T., Derijard B., Davis R.J.. The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1. These data demonstrate that the nucleus is one target of the p38 MAP kinase signal transduction pathway.. Mol. Cell. Biol. 16:1247-1255(1996) [PubMed] [Europe PMC] ...

TY - JOUR. T1 - Activation of the Syk tyrosine kinase is insufficient for downstream signal transduction in B lymphocytes. AU - Hsueh, Robert C.. AU - Hammill, Adrienne M.. AU - Lee, Jamie A.. AU - Uhr, Jonathan W.. AU - Scheuermann, Richard H.. PY - 2002/12/6. Y1 - 2002/12/6. N2 - Background: Immature B lymphocytes and certain B cell lymphomas undergo apoptotic cell death following activation of the B cell antigen receptor (BCR) signal transduction pathway. Several biochemical changes occur in response to BCR engagement, including activation of the Syk tyrosine kinase. Although Syk activation appears to be necessary for some downstream biochemical and cellular responses, the signaling events that precede Syk activation remain ill defined. In addition, the requirements for complete activation of the Syk-dependent signaling step remain to be elucidated. Results: A mutant form of Syk carrying a combination of a K395A substitution in the kinase domain and substitutions of three phenylalanines (3F) ...

Clear protocols for the study of membrane lipid properties, cellular transport or signal transduction are presented in this manual. Following a short introduction to membrane lipids, techniques for the isolation and extraction of membrane fractions, the analysis of the lipid composition, lipid turnover, and the involvement in signal transduction as well as the preparation of liposomes are : Paperback.. Clear protocols for the study of membrane lipid properties, cellular transport or signal transduction are Manual on Membrane Lipids. Authors: Prasad, Rajendra Free Preview.. Buy this book eB08 About this book. Clear protocols for the study of membrane lipid properties, cellular transport or signal transduction are presented in this manual. Following a short introduction to membrane lipids, techniques for the isolation and extraction of membrane fractions, the analysis of the lipid composition, lipid turnover, and the involvement in signal transduction as well as the preparation of liposomes are ...

TY - JOUR. T1 - Sensory Signaling-Dependent Remodeling of Olfactory Cilia Architecture in C. elegans. AU - Mukhopadhyay, Saikat. AU - Lu, Yun. AU - Shaham, Shai. AU - Sengupta, Piali. PY - 2008/5/13. Y1 - 2008/5/13. N2 - Nonmotile primary cilia are sensory organelles composed of a microtubular axoneme and a surrounding membrane sheath that houses signaling molecules. Optimal cellular function requires the precise regulation of axoneme assembly, membrane biogenesis, and signaling protein targeting and localization via as yet poorly understood mechanisms. Here, we show that sensory signaling is required to maintain the architecture of the specialized AWB olfactory neuron cilia in C. elegans. Decreased sensory signaling results in alteration of axoneme length and expansion of a membraneous structure, thereby altering the topological distribution of a subset of ciliary transmembrane signaling molecules. Signaling-regulated alteration of ciliary structures can be bypassed by modulation of ...

This course will discuss the basic concepts of cellular signal transduction. The role of Signal transduction pathways involving (receptor) kinases, G-protein coupled receptors, adhesion receptors, cytokine receptors, and nuclear hormone receptors in disease development, progression and drug development is discussed.. Disease development and progression is largely due to the activation and or modulation of cellular signaling. Mutations in signaling pathways that drive cell proliferation are key to cancer development and progression. In atherosclerosis, immune signaling is essential to promote plaque formation. Given the involvement of perturbed signaling in disease, components of signaling networks are important candidate drug targets. The course will discuss the concepts of cellular signal transduction and focus on (receptor) kinases, G-protein coupled receptors, cytokine receptors, and nuclear hormone receptors. We will discuss how these receptors are activated and which downstream signaling ...

Mechanical strain plays a significant role in the regulation of bone matrix turnover, which is mediated in part by matrix metalloproteinase (MMP)-13 and tissue inhibitors of matrix metalloproteinase (TIMP)-1. However, little is known about the correlation between mechanical strain and osteoblastic cell activities, including extracellular matrix (ECM) metabolism. Herein, we determined the effect of different magnitudes of cyclic tensile strain (0%, 6%, 12%, and 18%) on MMP-13 and TIMP-1 mRNA and protein expression in MC3T3-E1 osteoblasts. Furthermore, we employed specific inhibitors to examine the role of distinct signal transduction pathways known to mediate cellular responses to mechanical strain. We identified a magnitude-dependent increase in MMP-13 and TIMP-1 mRNA and protein levels in response to mechanical strains corresponding to 6%, 12%, and 18% elongation. The strain-induced increases in MMP-13 and TIMP-1 mRNA expression were inhibited by PD098059 and cycloheximide, respectively. Our results

TY - JOUR. T1 - Integrin signaling via the PI3-kinase-Akt pathway increases neuronal resistance to glutamate-induced apoptosis. AU - Gary, Devin S.. AU - Mattson, Mark P.. PY - 2001. Y1 - 2001. N2 - Integrins are integral membrane proteins that mediate adhesive interactions of cells with the extracellular matrix and with other cells. Integrin engagement results in activation of intracellular signaling cascades that effect several different cellular responses including motility, proliferation and survival. Although integrins are known to provide cell survival signaling in various types of non-neuronal cells, the possibility that integrins modulate neuron survival has not been explored. We now report data demonstrating a neuroprotective function of integrins in embryonic hippocampal neurons. Neurons grown on laminin, an integrin ligand, exhibit increased resistance to glutamate-induced apoptosis compared with neurons grown on polylysine. Neurons expressed integrin β1 and treatment of cultures ...

Title: Molecular Mechanisms of Bcl10-Mediated NF-kappaB Signal Transduction Author: Felicia D. Langel, Ph.D., 2006 Directed by: Brian C. Schaefer, Ph.D., Assistant Professor, Department of Microbiology and Immunology Bcl10 is a key signaling intermediate in the TCR-to-NF-?B pathway in T lymphocytes. It is currently believed that, once activated, Bcl10 functions within a multiprotein signaling complex that activates the IKK complex. Bcl10 is thought to regulate this signaling complex, but how it transmits its signal through the complex is unknown. A thorough knowledge of Bcl10 biology is critical to understanding how Bcl10 functions and how it regulates its binding partners. In this study, we used mutational analysis, molecular imaging, biochemistry, and computer/bioinformatics modeling to elucidate a structure and function for Bcl10. From our data, we identified a novel binding site for MALT1 within the Bcl10 protein, hypothesized that this site is completely separate and distinct from the ...

Traditionally, reactive oxygen species (ROS) have been regarded as toxic by-products of aerobic metabolism. However, in recent years it has become apparent that plants actively produce ROS as signalling molecules. ROS are able to mediate adaptive responses to various environmental stresses as well as processes such as stomatal closure and development. Downstream signalling events that are modulated by ROS include calcium mobilisation, protein phosphorylation and gene expression. This study investigated signalling proteins acting downstream of ROS, in order to understand how ROS are perceived and transduced to elicit such a wide range of responses. To establish a molecular profile provoked by ROS, a microarray experiment of Arabidopsis plants exposed to exogenous H(_2)O(_2) was analysed. Of the 895 differentially expressed transcripts, a substantial proportion had predicted functions in cell rescue and defence, including heat shock, disease resistance and antioxidant genes. Genes encoding ...

TY - JOUR. T1 - Lipid rafts are required for efficient signal transduction by CD1d. AU - Park, Yoon Kyung. AU - Lee, Joong Won. AU - Ko, Young Gyu. AU - Hong, Seokmann. AU - Park, Se Ho. N1 - Funding Information: The authors thank Dr. Albert Bendelac for critical reading of the manuscript and for providing αGalCer. This work was supported by a Rheumatism Research Center Grant (R11-2002-003) from the Korea Science and Engineering Foundation (to S.-H.P), and by a grant from the 21C frontier for the functional proteomics (FPR-02-A-5 to Y.-G.K).. PY - 2005/2/25. Y1 - 2005/2/25. N2 - Plasma membranes of eukaryotic cells are not uniform, possessing distinct cholesterol- and sphingolipid-rich lipid raft microdomains which constitute critical sites for signal transduction through various immune cell receptors and their co-receptors. CD1d is a conserved family of major histocompatibility class I-like molecules, which has been established as an important factor in lipid antigen presentation to natural ...

Strand breaks in cellular DNA occur continuously as a consequence of normal processes such as recombination or the infliction of DNA damage. DNA damage triggers several signal transduction pathways that lead either to damage repair coupled with attenuation of cell cycle progression, or to programmed cell death (apoptosis). A junction of such pathways is controlled by the transcription factor p53. After DNA damage, the amount of p53 in cells is increased through posttranscriptional mechanisms and its transactivation activity is enhanced, leading to the activation of downstream genes (1).. The genetic disorder A-T results in genome instability, cerebellar and thymic degeneration, immunodeficiency, gonadal dysgenesis, radiation sensitivity, and predisposition to cancer. A-T cells exhibit acute sensitivity to ionizing radiation and radiomimetic chemicals, and their cell cycle checkpoints fail to be activated after treatment with these agents (2). The responsible gene, ATM, encodes a 370-kD protein ...

Canonical WNT signals are transduced through Frizzled (FZD) family receptor and LRP5/LRP6 co-receptor to upregulate FGF20, JAG1, DKK1, WISP1, CCND1 and MYC genes for cell-fate determination, while non-canonical WNT signals are transduced through FZD family receptor and ROR2/PTK7/RYK co-receptor to activate RHOA/RHOU/RAC/CDC42, JNK, PKC, NLK and NFAT signaling cascades for the regulation of tissue polarity, cell movement, and adhesion. We previously reported molecular cloning and characterization of human FZD5, which showed six amino-acid substitutions with human Hfz5. FZD5, functioning as WNT5A receptor, is the key molecule in the fields of oncology, regenerative medicine, cardiology, rheumatology, diabetology, and gastroenterology. Here, comparative integromics analyses on FZD5 orthologs were performed by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee FZD5 and cow Fzd5 genes were identified within NW_104292.1 and AC166656.2 genome sequences, respectively. FZD5 ...

The previous studies have shown that HCMV infection initiates a novel signal transduction pathway that leads to the induction of ISGs (35, 36). Later, it was discovered that the HCMV envelope glycoproteins, gB and gH, and subsequent virion fusion are required for this virus-induced activation (3, 19, 25). In this study, we demonstrated that ISRE and GAS elements are HCMV response sites (VRS). A number of cellular proteins are activated after HCMV infection that specifically interact with the VRS. These proteins have molecular masses between 19 and 41.7 kDa.. It was interesting and unexpected to determine that both ISRE and GAS elements, in fact, form identical complexes with HCMV-activated proteins. The ISRE normally interacts with IFN-α or -β-activated complexes or ISGF-3 containing Stat1, Stat2, and IRF-9 (p48). GAS normally interacts with the IFN-γ-activated Stat1 homodimer (6, 7). The fact that HCMV-activated complexes recognize both ISRE and GAS elements suggests that either a single ...

TY - JOUR. T1 - Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade. AU - Hyman, Joel M. AU - Firestone, Ari J. AU - Heine, Vivi M. AU - Zhao, Yun. AU - Ocasio, Cory A. AU - Han, Kyuho. AU - Sun, Mark. AU - Rack, Paul G. AU - Sinha, Surajit. AU - Wu, Jason J. AU - Solow-Cordero, David E. AU - Jiang, Jin. AU - Rowitch, David H. AU - Chen, James K. PY - 2009/8/18. Y1 - 2009/8/18. N2 - Inappropriate activation of the Hedgehog (Hh) signaling pathway has been implicated in a diverse spectrum of cancers, and its pharmacological blockade has emerged as an anti-tumor strategy. While nearly all known Hh pathway antagonists target the transmembrane protein Smoothened (Smo), small molecules that suppress downstream effectors could more comprehensively remediate Hh pathway-dependent tumors. We report here four Hh pathway antagonists that are epistatic to the nucleocytoplasmic regulator Suppressor of Fused [Su(fu)], including two that can inhibit Hh target gene expression ...

The CssRS two-component system responds to heat and secretion stresses in Bacillus subtilis by controlling expression of HtrA and HtrB chaperone-type proteases and positively autoregulating its own expression. Here we report on the features of the CssS extracellular loop domain that are involved in signal perception and on CssS subcellular localization. Individual regions of the CssS extracellular loop domain contribute differently to signal perception and activation. The conserved hydrophilic 26-amino-acid segment juxtaposed to transmembrane helix 1 is involved in the switch between the deactivated and activated states, while the conserved 19-amino-acid hydrophobic segment juxtaposed to transmembrane 2 is required for signal perception and/or transduction. Perturbing the size of the extracellular loop domain increases CssS kinase activity and makes it unresponsive to secretion stress. CssS is localized primarily at the septum but is also found in a punctate pattern with lower intensity ...

9. An apparatus for simulating a therapeutic manipulation comprising: an elongate body having an axial cavity; an elongate reciprocating body adapted to fit into the axial cavity of the elongate body; a biasing member adapted to fit within the axial cavity of the elongate body, the biasing member being further adapted to be disposed along an axis of the axial cavity and bias the elongate reciprocating body to a first position relative to the axis of the axial cavity; a rod attached to the elongate body and disposed along the axis of the axial cavity; a sensing system disposed within the elongate reciprocating body and configured to measure a relative displacement of the rod and the elongate reciprocating body, the sensing system including a plurality of photo interrupters disposed along the axis of the axial cavity of the elongate body and configured to generate first position signals that identify different fixed positions of the rod, and an optical sensor disposed along the axis of the axial ...

Short Talk: Cell Basal Polarity Complex Scribble Is Required for Leukemic Initiation and Propagation through Negative Regulation of Apical Polarity Complex Activator Cdc42 and Hypoxia Inducing Factor-1α ...

Despite the fact that ExoS induction of apoptosis is independent of de novo gene expression, the patterns of differentially altered gene expression observed in our study could be important signatures for the activation or stimulation of specific signal transduction pathways, such as JNK activation. An earlier report studying gene expression in the A549 lung pneumocyte cell line after exposure to P. aeruginosa identified host genes that are preferentially expressed upon infection by P. aeruginosa (39). Several of those genes are also seen in our present study, such as c-Jun in particular (data not shown).. One effect of ExoS ADPRT activity is to inhibit activation of cell survival pathways. The ExoS-dependent inhibition of ERK1/2 is consistent with previous work from other investigators (30). Although the specific contribution of p38 activation to survival in HeLa cells is unknown, p38 has been implicated in both apoptosis and anti-apoptosis signaling (31). Thus, inhibition of p38 phosphorylation ...

Basic molecular mechanisms of cell surface receptors that mediate transmembrane signals can be elucidated by integrating information from multiple interdisciplinary approaches. Our studies focus on the receptor (FceRI) for immunoglobulin E (IgE) that plays a central role in the allergic response and serves as a model for other types of immune receptors. Binding and cross-linking of IgE-FceRI complexes by antigen initiates signal transduction resulting in cell activation and release of chemical mediators.. We measure kinetics and thermodynamics of binding and cross-linking between cell-bound IgE and structurally defined ligands with fluorescence methods and analyze with realistic theoretical models to determine features that are critical for signaling. We employ quantitative fluorescence microscopy, including confocal imaging and total internal reflection fluorescence (TIRF) microscopy, to monitor changes in the distribution and dynamics of the receptor and signaling components (and genetically ...

Background B cells are essential regulators and effectors of adaptive and innate immune system responses, autoimmunity and inflammation, for example in anti-NMDA-receptor (NMDAR) encephalitis. IL-10 creating B cells after BCR/Compact disc40 excitement. Conclusions noncompetitive NMDAR antagonists attenuate BCR and Toll-like receptor 4 (TLR4) B-cell signaling and effector function and may foster IL-10 creation. Consequently, NMDAR antagonists may be beneficial to focus on B cells in autoimmune illnesses or pathological systemic swelling. The drugs extra unwanted effects on B cells is highly recommended in remedies of neuronal disorders with NMDAR antagonists. [29]. Furthermore, although actions of noncompetitive NMDAR antagonists on memory space B cells isnt looked into, pharmacological modulation of memory space B-cell differentiation or supplementary B-cell responses could be envisaged. Since particular blockade of Kv1.3 and KCa3.1 stations leads to immunosuppression of B and T cells [54, ...

Natural Killer (NK) cell responses are shaped by the integration of signals transduced from multiple activating and inhibitory receptors at their surface. Biochemical and genetic approaches have identified most of the key proteins involved in signal integration but a major challenge remains in understanding how the spatial and temporal dynamics of their interactions lead to NK cells responding appropriately when encountering ligands on target cells. Well over a decade of research using fluorescence microscopy has revealed much about the architecture of the NK cell immune synapse - the structured interface between NK cells and target cells - and how it varies when inhibition or activation is the outcome of signal integration. However, key questions - such as the proximity of individual activating and inhibitory receptors - have remained unanswered because the resolution of optical microscopy has been insufficient, being limited by diffraction. Recent developments in fluorescence microscopy have broken

Significant pharmaceutical innovations and progresses have occurred in oncology treatments and patients management. Recent signal transduction inhibitor agents having a strong anti-tumour specificity are able to disrupt signal pathways mediating cancer cell proliferation and efficiently prevent tumour growth. Signal transduction inhibitors include imatinib, sunitinib, nilotinib, dasatinib, sorafenib and other tyrosine kinase blockers currently under investigation. But other chemotherapeutic drugs such as antimetabolites (methotrexate, 5-Fluorouracil), mitotic spindle inhibitors (vincristine, vinorelbine), antibiotic inhibitors of topoisomerases (etoposide, topotecan) etc. are also increasingly used in oncology. As a consequence, cancer patients are living longer, and the amount of consumption of these classes of drugs has grown accordingly. In parallel, the amount of anticancer drug residues released into the environment has increased. Indeed, most anticancer drugs are eliminated by urines or ...

The current standard of care for malignant glioma is initial treatment with radiation therapy combined with TMZ; however, malignant gliomas usually recur with a median time to progression of approximately 7 months [1]. Two decades of molecular studies have identified important genetic events such as dysregulation of growth factor signaling via amplification or mutation of receptor tyrosine kinase genes; activation of PI3K pathway; and inactivation of p53 and Rb tumor suppressor pathways [2]. In this study, we tried to identify the potential targets for counteracting the pro-survival signaling implicated in radioresistance of malignant glioma cells and to get insight into potential strategies to improve the therapeutic outcome of radiotherapy and TMZ in the management of GBM.. Inhibition of signal transduction pathways may provide the basis for a new paradigm of GBM therapy, based on the fact that most human gliomas exhibit aberrant activation of a pro-survival/pro-growth signaling network. EGFR ...

TY - JOUR. T1 - Mutants of basic fibroblast growth factor identity different cellular response programs. AU - Leenders, W.P.J.. AU - van Hinsbergh, V.W.M.. AU - van Genesen, S.T.. AU - Schoenmakers, J.G.G.. AU - Zoelen, E.J.J.. PY - 1997. Y1 - 1997. U2 - 10.3109/08977199709021521. DO - 10.3109/08977199709021521. M3 - Article. VL - 14. SP - 213. EP - 228. JO - Growth Factors. JF - Growth Factors. SN - 0897-7194. ER - ...

TY - JOUR. T1 - Signal transduction pathways of GM-CSF in neural cell lines. AU - Choi, Jung Kyoung. AU - Choi, Byung Hyune. AU - Ha, Yoon. AU - Park, Hyeonseon. AU - Yoon, Seung Hwan. AU - Park, Hyung Chun. AU - Park, So Ra. N1 - Funding Information: This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A050082). PY - 2007/6/15. Y1 - 2007/6/15. N2 - GM-CSF is recently being suggested to play important role(s) in the nervous system. Present study was intended to understand signal transduction pathways of GM-CSF in human neuroblastoma (SK-N-(BE)2) and glioblastoma (A172) cell lines. The expression of GM-CSF receptors on the surface of these cells was confirmed by immunocytochemistry, Western blot analysis and RT-PCR. When treated for 10 min, GM-CSF activated the signal transducer and activator of transcription 5 (STAT5) and extracellular signal regulated kinase (ERK) in both cell lines. However, Janus kinase 2 (JAK2) was activated ...

ScienceDaily (July 12, 2011) - Research to be presented at the upcoming annual meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, finds that alterations of meal-related gut hormone signals may contribute to the overall effects of exercise to help manage body weight.. Regular exercise is important in maintaining low body weight and also is known to facilitate weight loss in obese subjects. Running exercise is known to increase sensitivity to leptin, a hormone released from fat cells that inhibits food intake. The authors new study reveals additional mechanisms that contribute the beneficial effects of exercise.. Gut hormones are released before and after a meal to initiate and terminate food intake. The authors measured gut hormone release after a palatable tasty meal before and after rats exercised in running wheels. In rats with a lot of running wheel experience, consuming a tasty meal led to ...

Upon immune cell activation with antigen, growth factors, or other stimuli, the cytoskeleton undergoes extensive reorganization to elicit a cellular response. The cytoskeleton, consisting of microtubules and actin, is a highly organized network regulated by various signal transduction pathways. Specifically, Rho GTPases (RhoA, Rac1 and Cdc42) regulate the cytoskeleton, albeit through different pathways. p21-activated kinases (Pak) are serine/threonine kinases directly bound and activated by Rac1 and Cdc42. There are 6 Pak isoforms separated into 2 groups (groups I&II) in this family of kinases, and only recently have isoform specificities been identified by the use of genetically-engineered mouse models deleted for individual isoforms. In this dissertation we sought to identify if differences exist between Pak1 and Pak2 in immune function, in particular how they differ in regulation of the cytoskeleton reorganization required for immune cell function. Using primary bone marrow derived mast cells, an

TY - JOUR. T1 - Phosphoproteins involved in bacterial signal transduction. AU - Stock, Ann. AU - Wylie, D. C.. AU - Mottonen, J. M.. AU - Lupas, A. N.. AU - Ninfa, E. G.. AU - Ninfa, A. J.. AU - Schutt, C. E.. AU - Stock, J. B.. PY - 1988. Y1 - 1988. UR - http://www.scopus.com/inward/record.url?scp=0024155286&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0024155286&partnerID=8YFLogxK. U2 - 10.1101/sqb.1988.053.01.009. DO - 10.1101/sqb.1988.053.01.009. M3 - Article. C2 - 3076087. AN - SCOPUS:0024155286. VL - 53. SP - 49. EP - 57. JO - Cold Spring Harbor Symposia on Quantitative Biology. JF - Cold Spring Harbor Symposia on Quantitative Biology. SN - 0091-7451. IS - 1. ER - ...

Bioorganic Chemistry of Biological Signal Transduction by Herbert Waldmann (Editor) starting at $10.00. Bioorganic Chemistry of Biological Signal Transduction has 2 available editions to buy at Alibris

Kawakami, Y.; Capdevila, J.; Buscher, D.; Itoh, T.; Rodriguez Esteban, C.; Ng, J.; Izpisua Belmonte, J.C.rlos, 2001: WNT signals control FGF-dependent limb initiation and AER induction in the chick embryo

A heart attack occurs when a blood clot forms in a coronary artery depriving blood flow from a region of the heart, a condition termed ischemia. Current therapy is to reopen the artery but blood flow is seldom restored before a significant amount of the heart muscle has died. Because lost heart muscle cannot be regenerated the patient is left with a weakened heart and heart failure often occurs. Our research is directed toward identifying therapies that prevent cell death in ischemic heart. We have found that population of Gi-coupled receptors prior to ischemia makes the heart very resistant to cell death. Our current research is directed at mapping the complex signal transduction pathway involved. To date we have found that population of surface receptors with bradykinin or opioids, through their G-proteins, cause transactivation of epidermal growth factor receptors. That in turn activates PI3 kinase which causes activation of Akt through phosphorylation. Akt activation results ultimately in ...

Statins are the most commonly prescribed drugs worldwide, are cholesterol lowering agents used to manage and prevent cardiovascular and coronary heart diseases. Recently a multifaceted actions in different physiological and pathological conditions has been also proposed for statins such as antiiflammation, neuroprotection etc. Statins have been shown to act through cholesterol dependant & independent mechanisms which are able to affect several tissue functions and modulate specific signal transduction pathways. Here we review the pharmacology of statins, providing a comprehensive update of the current knowledge of their effects on tissues, biological processes & pathological conditions; but statins are now becoming recognized as powerful anti-inflammatory agents that exert beneficial effects beyond low density lipoprotein cholesterol reduction.

The c-Jun NH2-terminal kinases (JNK) are evolutionarily conserved serine/threonine protein kinases that are activated by proinflammatory cytokines, environmental stress, and genotoxic agents. These kinases play key regulatory roles within a cell by coordinating signals from the cell surface to nuclear transcription factors. JNK phosphorylates the amino terminal domain of all three Jun transcription factors (JunB, c-Jun and JunD) all members of the AP-1 family. The activated transcription factors modulate gene expression to generate appropriate biological responses, including cell migration, proliferation, differentiation and cell death. The role of the JNK signaling pathway in cell death/apoptosis is controversial, both pro-apoptotic and pro-survival roles have been attributed to JNK. The mechanism that enables the JNK signaling pathway to mediate both apoptosis and survival is unclear. The aim of this study is to examine the role of TNF-stimulated JNK activation on cell survival. The proinflammatory

MAPK signaling cascades seem to play divergent roles in the prostate gland. Significant differences have been observed in the activation pattern of all MAPK network components in prostate epithelial and stromal cells, under normal and pathologic conditions. Modulation of MAPK pathways has been shown in several prostate cancer cell lines by growth factors, cytokines, and a variety of agents that control growth and apoptosis of prostate cancer cells. However, structure and function of MAPK signal transduction pathways have not been thoroughly defined in prostate carcinogenesis.. The prostate is a heterogeneous gland comprising several cell types, which regulate each others function by paracrine mechanisms. Hence, it is important to decipher the role played by MAPK signal transduction pathways in mediating the interaction between various neighboring prostate cell types. A diverse array of signaling cascades have been identified as activating elements upstream of the MAPK circuitry. In-depth ...

Aberrant activity of the MAP and PI3 kinases is implicated in many forms of cancer. The ability to gather quantifiable information on the activation state of these kinases from limited in-vitro and in-vivo tumor samples would accelerate drug development and ultimately, the treatment of cancer. In this BioScale poster, presented at ELRIG Drug Discovery 2012, non-optical acoustic membrane microparticle (AMMP®) technology was used to quantitate the activity state of multiple kinases including EGFR,

Despite extensive studies on the involvement of farnesol in C. albicans germination and biofilm formation, the characterization of a physiological role for farnesol and its implications on the fungal cell cycle have been lacking. As eukaryotic cells, fungal and human cells share similar metabolic pathways. Hence, the inhibitory effect of farnesol on C. albicans could also involve cellular signal transduction pathways similar to the apoptotic process described in mammalian cells. Therefore, in order to elucidate the mechanisms underlying farnesol cytotoxicity and its possible involvement in an apoptotic process in C. albicans, a global two-dimensional proteomic approach was utilized to unravel altered protein expression following farnesol treatment. In addition, an assessment of standard apoptotic markers using fluorescent microscopy and gene expression analysis was also undertaken.. Proteomic analysis of the farnesol-exposed cells revealed a significant number of proteins to be differentially ...

Activation of the Toll-like receptor (TLR) family of innate immune sensors stimulates multiple signal transduction pathways. Previous studies have suggested that TLR2, TLR4 and TLR9 induce serine phosphorylation of Signal Transducers and Activators of Transcription-1 (STAT1) at residue 727 (S727), a …

The transforming growth factor β (TGFβ) superfamily of signal transduction molecules plays crucial roles in the regulation of cell behavior. TGFβ regulates gene transcription through Smad proteins and signals via non-Smad pathways. The TGFβ pathway is strictly regulated, and perturbations lead to tumorigenesis. Several pathway components are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. Smurfs are well known negative regulators of TGFβ, which function as E3 ligases recruited by adaptors such as I-Smads. TGFβ signaling can also be enhanced by E3 ligases, such as Arkadia, that target repressors for degradation. It is becoming clear that E3 ligases often target multiple pathways, thereby acting as mediators of signaling cross-talk. Regulation via ubiquitination involves a complex network of E3 ligases, adaptor proteins, and deubiquitinating enzymes (DUBs), the last-mentioned acting by removing ubiquitin from its targets. Interestingly, also non-degradative ...

Purification and characterization of two isoenzymes of DL-glycerol-3-phosphatase from Saccharomyces cerevisiae. Identification of the corresponding GPP1 and GPP2 genes and evidence for osmotic regulation of Gpp2p expression by the osmosensing mitogen-activated protein kinase signal transduction pathway ...

Post-translational modification (PTM) of proteins regulates many biological phenomena [1]. Among the several kinds of PTM, phosphorylation affects enzymatic activity, conformations, interactions, degradation, and localization of proteins, among other effects [2-4]; one of the critical roles of phosphorylation is in the control of protein signaling [5]. More than 500 protein kinases are thought to regulate protein signaling in humans [6]. In protein signaling, various reaction cascades transmit and amplify signals in a highly regulated manner by means of reversible site-specific protein phosphorylation [5]. Kinases recognize the specific surrounding sequences of phosphosites when they phosphorylate their targets, and the majority of the identified kinases are thought to have their own unique target sequences, which are known as motif sequences [7].. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), combined with phosphopeptide enrichment technology [8], is a powerful ...

Read The woody plant poplar has a functionally conserved salt overly sensitive pathway in response to salinity stress, Plant Molecular Biology on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.