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 ...
Title: Signal Transduction Inhibitors as Radiosensitizers. VOLUME: 2 ISSUE: 6. Author(s): A. Tenzer, D. Zingg, O. Riesterer, V. Vuong, S. Bodis and M. Pruschy. Affiliation:Laboratory for Molecular Radiobiology, Dept. Radiation Oncology, University Hospital Zurich, CH-8091 Zurich, Switzerland.. Abstract: 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 ...
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 ...
Abstract ABSTRACT The role of riboflavin as an elicitor of systemic resistance and an activator of a novel signaling process in plants was demonstrated. Following treatment with ri..
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 ...
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 ...
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, ...
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 ...
Thank you for your interest in spreading the word about Biochemical Society Transactions.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.. ...
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)
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 ...
Proteins used in signal transduction pathways are commonly found in different cell types and organs. However, specific proteins whose expression is highly restricted are also utilized for allowing discrete responsiveness to signals that are otherwise ignored by other cells. How the brain uses common and specific signal proteins for communication within and beyond the cerebrum has been an area of intense study. A new book concentrates on the signaling that occurs in the brain under normal and pathological conditions--memory, apoptosis, neurodegeneration, depression, and drug dependence--and is filled with chapters written by experts in neurobiology and neurophysiology. Bryan Roth reviews the book and discusses in detail several chapters that may lead to promising future research. ...
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...
Health, ...HOUSTON - Two signaling pathways essential to normal human development...This newly characterized interaction involves three signaling componen... These findings highlight the importance of Wnt-independent and non-ca... Wnt Signaling and Cell-to-Cell Adhesion ...,Crosstalk,between,critical,cell-signaling,pathways,holds,clues,to,tumor,invasion,and,metastasis,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
This chapter describes the normal mechanisms whereby fluid is secreted and absorbed along the length of the gastrointestinal tract, and the regulatory pathways that govern these processes. The chapter discusses the precise transport mechanisms that mediate the flux of electrolytes and other solutes in the small and large intestines. All the transport mechanisms discussed in the chapter are active, in that they result in the transepithelial transport of the solute of interest against existing electrochemical gradients. Intestinal epithelial ion transport is regulated via complex pathways that are still not fully understood. Regulation can be divided into two complementary mechanisms: (i) an intercellular mechanism consisting of stimulation of the epithelium by mediators released from nerves, endocrine cells, and other effector cells and (ii) an intracellular mechanism where second messengers initiate signal transduction pathways within the epithelial cells themselves. Ultimately, regulatory mechanisms
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 ...
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 ...
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 ...
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 ...
The Mouse G Protein Coupled Receptors 384HT RT Profiler PCR Array profiles the expression of a comprehensive panel of 370 genes encoding the most important G Protein Coupled Receptors (GPCR). GPCR regulate a number of normal biological processes and play roles in the pathophysiology of many diseases upon dysregulation of their downstream signal transduction activities. As a result, they represent 30 percent of the targets for all current drug development. Developing drug screening assays requires a survey of which GPCR the chosen cell-based model system expresses, to determine not only the expression of the target GPCR, but also related GPCR to assess off-target side effects. Expression of other unrelated GPCR (even orphan receptors whose ligand are unknown) may also correlate with off-target side effects. The ligands that bind and activate the receptors on this array include neurotransmitters and neuropeptides, hormones, chemokines and cytokines, lipid signaling molecules, light-sensitive ...
The unfolded protein response (UPR) is a cell-signaling system that detects the accumulation of unfolded protein within the endoplasmic reticulum (ER) and initiates a number of cellular responses to restore ER homeostasis. The presence of unfolded protein is detected by the ER-luminal sensor domains of the three UPR-transducer proteins IRE1, PERK, and ATF6, which then propagate the signal to the cytosol. In this review, we discuss the various mechanisms of action that have been proposed on how the sensor domains detect the presence of unfolded protein to activate downstream UPR signaling.
Cytoplasmic Janus protein tyrosine kinases (JAKs) are crucial components of diverse signal transduction pathways that govern cellular survival, proliferation, differentiation and apoptosis. Evidence to date, indicates that JAK kinase function may integrate components of diverse signaling cascades. While it is likely that activation of STAT proteins may be an important function attributed to the JAK kinases, it is certainly not the only function performed by this key family of cytoplasmic tyrosine kinases. Emerging evidence indicates that phosphorylation of cytokine and growth factor receptors may be the primary functional attribute of JAK kinases. The JAK-triggered receptor phosphorylation can potentially be a rate-limiting event for a successful culmination of downstream signaling events. In support of this hypothesis, it has been found that JAK kinase function is required for optimal activation of the Src-kinase cascade, the Ras-MAP kinase pathway, the PI3K-AKT pathway and STAT signaling following the
Cells continually make decisions about their fate: growth, death or differentiation. These decisions frequently are determined by signal transduction cascades of small GTP-binding proteins and protein kinases, which are activated in response to extracellular signals. Our laboratory utilizes tools of cell biology, protein chemistry and molecular biology to understand how signal transduction controls cell growth and apoptosis, how these controls are altered in cancer, and how this information can be used to improve cancer treatment. MAP kinases: regulation and function. MAP Kinase cascades are among the most thoroughly studied of signal transduction systems, and have been shown to participate in a diverse array of cellular programs including cell differentiation, cell movement, cell division and cell death. They typically are organized in a three-kinase architecture consisting of a MAP Kinase (MAPK), a MAP Kinase activator (MEK) and a MEK activator (MEKK). Transmission of signals is achieved by ...
p53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated genes. This results in three major outputs; cell cycle arrest, cellular senescence or apoptosis. Other p53-regulated gene functions communicate with adjacent cells, repair the damaged DNA or set up positive and negative feedback loops that enhance or attenuate the functions of the p53 protein and integrate these stress responses with other signal transduction pathways ...
p53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated genes. This results in three major outputs; cell cycle arrest, cellular senescence or apoptosis. Other p53-regulated gene functions communicate with adjacent cells, repair the damaged DNA or set up positive and negative feedback loops that enhance or attenuate the functions of the p53 protein and integrate these stress responses with other signal transduction pathways ...
Numerous studies have reported that engagement of TLR proteins leads to the activation of NF-κB and MAP kinases. These activation events are elicited upon engagement of TLR2, TLR4, and TLR9 by their distinct agonists,9 12 21 suggesting that they are shared responses that use a common signal transduction pathway. This pathway is likely to be mediated by MyD88, and the downstream signalling components IL1 receptor associated kinases and TRAF6 (reviewed by Means et al 2 and ONeill and Greene7). Published studies have shown that engagement of TLR4, but not TLR2 and TLR9, can also lead to the activation of an MyD88 independent pathway and then to NF-κB and MAP kinase activation.26 27 Together, these reports show that TLR proteins use both shared and unique signal transduction pathways. Here we have extended these findings by identifying a cellular response that is induced by different TLR agonists, and a distinct response that is restricted to specific TLR proteins. Specifically, both TLR2 and ...
TY - JOUR. T1 - Using 3D animations to teach intracellular signal transduction mechanisms. T2 - Taking the arrows out of cells. AU - Buchanan, M. Flint. AU - Carter, William C.. AU - Cowgill, Lari M.. AU - Hurley, David J.. AU - Lewis, Stephen J.. AU - MacLeod, James N.. AU - Melton, Thel R.. AU - Moore, James N.. AU - Pessah, Isaac N. AU - Roberson, Mark. AU - Robertson, Thomas P.. AU - Smith, Malcolm L.. AU - Vandenplas, Michel L.. PY - 2005/3. Y1 - 2005/3. N2 - Traditional methods of teaching intracellular biological processes and pathways use figures or flowcharts with the names of molecules linked with arrows. Many veterinary students, presented with such material, simply memorize the names or chemical structures of the molecules and are then likely to forget the material once the examination is completed. To address this problem, the authors designed, created, and field-tested new teaching media that incorporate realistic three-dimensional (3D) animations depicting the dynamic changes that ...
Diversity of G-Protein-Coupled Receptor Signal Transduction Pathways
Receptors coupled to heterotrimeric GTP-binding proteins (G-proteins) are integral transmembrane proteins that transduce extracellular signals to the cell interior. G-protein-coupled receptors exhibit a common structural motif consisting of seven membrane spanning regions. Receptor occupation promotes interaction between the receptor and the G-protein on the interior surface of the membrane. This induces an exchange of GDP for GTP on the G-protein α subunit and dissociation of the α subunit from the β γ heterodimer. Depending on its isoform, the GTP α subunit complex mediates intracellular signaling either indirectly by acting on effector molecules such as adenylate cyclase (AC) or phospholipase C (PLC), or directly by regulating ion channel or kinase function.
References:
Schoneberg, T., et al., Structural basis of G-protein-coupled receptor function. Mol. Cell. Endocrinol. 151, 181-193 (1999).
Research in our laboratory is focused on understanding the molecular mechanism of receptor-mediated signal transduction. All living cells monitor their surrounding environments and elicit appropriate responses to changing conditions. Such stimulus-response coupling is essential for numerous and diverse processes such as growth and development, metabolic regulation, and sensing. Signal transduction pathways, through which information is passed sequentially from one protein component to the next, provide the molecular mechanism for linking input signals to output responses. Despite great diversity in the types of stimuli and responses involved in different pathways, a limited number of fundamental molecular strategies are used for signal transduction. One such strategy is reversible covalent modification, a process that regulates the activities of proteins. Our laboratory is investigating this signaling mechanism from both structural and functional perspectives. Two-Component Signal Transduction ...
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.
... New tools to study in vivo functions of new genes and drug candidat...Stratagenes PathDetect in vivo signal transduction pathway reporting...Signal transduction is essential for cellular growth differentiation ...Many extracellular signals modulate cellula...,In,Vivo,Signal,Transduction,Pathway,Reporting,Systems,biological,advanced biology technology,biology laboratory technology,biology device technology,latest biology technology
The ordered, directional migration of T-lymphocytes is a key process during immune surveillance, and immune response. T-cell migration is a complex, highly coordinated process. This requires cell adhesion to the high endothelial venules or to the extracellular matrix by a series of surface receptor/ligand interactions involving adhesion molecules of the integrin family including lymphocyte function associated molecule-1 (LFA-1), phosphorylation- dependent signalling cascades and cytoskeletal rearrangements. Mechanisms that regulate T-cell migration are of considerable relevance for understanding the pathogenesis of various diseases including chronic inflammatory diseases such as inflammatory bowel disease and the inflammatory arthropathies ...
In this Focus Issue of Science Signaling, which complements the Science Special Issue on Gene Regulation (http://www.sciencemag.org/generegulation/), we examine the multilayered mechanisms that control how gene expression is turned on or off. Perspectives in this issue discuss how oncogenic Ras directs the silencing of tumor suppressor genes; how intrachromosomal looping brings enhancers and promoters together to stimulate gene expression; and how the abundance of a transcriptional coactivator affects nuclear receptor-mediated transcription.. ...
Therapeutic inhibition of the miR-34 family (miR-34a -b -c) or miR-34a only have emerged as encouraging strategies for the treating cardiac pathology. safety this approach will probably result in much less potential off-target results. Subsequently silencing of miR-34a only may be inadequate in configurations of founded cardiac pathology. We lately proven Cobicistat that inhibition from the miR-34 family members however not miR-34a only provided benefit inside a chronic style of myocardial infarction. Inhibition of miR-34 also attenuated cardiac redesigning and improved center function pursuing pressure overload nevertheless silencing of miR-34a only was not analyzed. The purpose of this research was to assess whether inhibition of miR-34a could attenuate cardiac redesigning inside a mouse model with pre-existing pathological hypertrophy. Mice had been put through pressure overload via constriction from the transverse aorta for a month and echocardiography was performed to verify remaining ...
This site contains prices and technical information for products manufactured and sold by LC Laboratories. LC Laboratories manufactures laboratory reagents used to study signal transduction processes in cells and tissues in biomedical research. Signal transduction comprises the process by which communications between cells in an organism are transmitted from the outside surface of the cells into internal regions. LC Labs' products, which are the highest quality and lowest priced in the market, are produced either by: 1) isolation and/or semi-synthetic modification of natural products using preparative liquid chromatography (HPLC); or 2) multi-step total synthesis.
I certify that my interest in, and any purchase and use of, LC Laboratories products is only for laboratory research at a qualified research institution, and is not related to use by a private individual or patient, nor for veterinary use ...
Fibroblast growth factors (FGF) are small polypeptide growth factors. Many FGFs bind to the heparan-like glycosaminoglycans of the extracellular matrix (ECM; ref. 1). From this reservoir, FGFs may act directly on target cells by binding to specific receptor tyrosine kinases and this binding induces receptor dimerization and activation, ultimately resulting in the activation of various signal transduction cascades (2, 3). Some FGFs are potent angiogenic factors, and most of them play important roles in embryonic development and wound healing (4, 5).. FGF signaling seems to play a role in tumor growth and angiogenesis, and autocrine FGF signaling may be particularly important in the progression of steroid hormone-dependent cancers to a hormone-independent state (6). FGFs secreted by tumors act, on the one hand, in an autocrine manner promoting tumor growth, and, on the other hand, in a paracrine manner on endothelial cells, thereby promoting tumor angiogenesis (7). Both FGF-2 and VEGF are known to ...
Proliferation in cardiac fibroblasts (CFs) can be induced by a wide variety of growth factors that recruit multiple signal transduction pathways, including mitogen-activated protein kinase, phosphatidylinositol 3-kinase and protein kinase C. As a family of dimeric phophoserine-binding proteins, 14-3-3s are associated with a multitude of proteins that regulate signal transduction, apoptosis and checkpoint control pathways. However, it remains unknown whether the 14-3-3 proteins play an active role in cardiac proliferation and alter their expression patterns in response to growth factors in CFs. R18 peptide, an isoform-independent 14-3-3 inhibitor, was used to disrupt 14-3-3 function by adenovirus-mediated transfer of R18-EYFP (AdR18). Our results demonstrate that the 14-3-3 isoforms gamma, zeta and epsilon were highly expressed in CFs and the expression of 14-3-3 epsilon was elevated following serum stimulation. Inhibition of 14-3-3 proteins by AdR18 potentiated mitogen-induced DNA synthesis in ...
Plant growth and development is controlled by various environmental cues that are sensed by the plant via various signal transduction pathways coupled to specific response. Some of these pathways are
Most hormones initiate a cellular response by initially combining with either a specific intracellular or cell membrane associated receptor protein. A cell may have several different receptors that recognize the same hormone and activate different signal transduction pathways, or alternatively different hormones and their receptors may invoke the same biochemical pathway. For many hormones, including most protein hormones, the receptor is membrane associated and embedded in the plasma membrane at the surface of the cell. The interaction of hormone and receptor typically triggers a cascade of secondary effects within the cytoplasm of the cell, often involving phosphorylation or dephosphorylation of various other cytoplasmic proteins, changes in ion channel permeability, or increased concentrations of intracellular molecules that may act as secondary messengers (e.g. cyclic AMP). Some protein hormones also interact with intracellular receptors located in the cytoplasm or nucleus by an intracrine ...
The PhoP binding pattern within the resA promoter is similar to other PhoP-regulated promoters(Liu, 1997; Liu and Hulett, 1997; 1998; Liu et al., 1998a, b), in that (i) both PhoP and PhoP∼P bind to these promoters; (ii) PhoP∼P extends the binding site further upstream and/or downstream, and has a higher binding affinity; and (iii) the core PhoP-binding region (region bound by PhoP and PhoP∼P) is located from about −22 to −60 in all these promoters(Liu and Hulett, 1998), including resA. A feature unique to the resA promoter among PhoP-regulated promoters is that it contains only two of the consensus PhoP binding repeats in the core binding region (Fig. 6), instead of at least four as seen in other Pho promoters studied. Ongoing expression and footprinting analyses of a site-specific mutagenized PhoP regulated promoter (S. Eder and F. M. Hulett, unpublished) indicate that PhoP binds to 6 bp repeated TT(A/T/C)ACA sequences separated by 4-5 bp, and that PhoP binding to one set of consensus ...
The role of TGF-β in breast cancer progression is unclear. TGF-β can display both tumor-suppressive and tumor-promoting effects. The hormonal influence on activation of the TGF-β system adds an additional layer of complexity. A central role in TGF-β signal transduction is played by the TGF-β receptors. TGF-β signals are mediated by an activated complex of TβRI and TβRII (8) . Downstream of the receptors different signal transduction pathways have been implicated in TGF-β signaling (26, 27, 28, 29, 30) .. Thus far only a few studies have examined the role of the TGF-β receptors in breast cancer tissues; none of these studies considered the influence of receptor expression on disease outcome. In this retrospective exploratory study we have therefore analyzed the expression of TβRI and TβRII in 246 human breast cancer tissues and adjacent normal tissues, and evaluated their association with prognosis. To assess hormonal influences on the TGF-β system we additionally included the ER ...
Author: 溫義輝, Title: Anti-sense morpholino oligonucleotide assay shows critical involvement for NF-jB activation in the production of Wnt-1 protein by HepG2 cells oncology implications, Category: 論文, Academic Year: 981, Department: 生物科技系, ViewId: 619
Many pathways activate NF‐κB by transducing signals to a core activation module consisting of the IKK complex, IκB, ubiquitylation machinery, proteasome, rel homo‐ or heterodimer and nuclear import factors. Pathway‐specific molecules function in the link between stimulus recognition and IKK complex activation in an interplay that must elicit an appropriate response to the stimulus, in part through the coordinate regulation of other transcription factor systems. In an effort to better understand the disparate mechanisms for NF‐κB activation, we have explored an expression cloning approach with the hope of finding new players, new mechanistic insights and, potentially, new pathways. To probe components used for lymphocyte signaling to NF‐κB, we screened a mouse thymus expression library and cloned the murine CARD11 cDNA.. Our data indicate that CARD11 functions in the activation of NF‐κB by TCR ligation and CD28 co‐stimulation. Expression of a CARD‐deleted CARD11 in Jurkat T ...
Signal transduction in human cells is based on complex networks and feedback loops of protein interactions. Despite widespread literature on signal transduction from individual cell membrane receptors, little is known about the cross-talk between receptor pathways. TCR ESC proteins, initially thought to be exclusive to TCR signalling, have been shown to transduce signals from diverse receptors. Both IFNαR and CXCR4 cross-talk with the TCR through the utilization of a common subset of proteins that comprise the TCR ESC [4-7]. The results of the present study demonstrated that α4β1 outside-in and TCR signalling pathways are also networked through the use of TCR ESC proteins. However, the present study revealed key differences in the activation of TCR ESC proteins between α4β1 outside-in and TCR signalling pathways. In TCR signalling, activated Lck recruits ZAP-70 to the TCR, resulting in ZAP-70 autophosphorylation at Tyr319, binding to Lck, and subsequent phosphorylation of ZAP-70 at Tyr493 ...
The transduction of biological signals depends on the spatial communication of conformational change. We report a synthetic mimic of this signal transduction process in which non-covalent binding induces a change in the position of equilibrium between two rapidly interconverting screw-sense conformers of a s
Evidence demonstrates that exogenously administered nitric oxide (NO) can induce insulin resistance in skeletal muscle. We have investigated the modulatory effects of two NO donors, S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and S-nitrosoglutathione (GSNO) on the early events in insulin signaling in rat skeletal myocytes. Skeletal muscle cells from 6-8 week old Sprague-Dawley rats were treated with SNAP or GSNO (25 ng/ml) in the presence or absence of glucose (25 mM) and insulin (100 nM). Cellular insulin receptor-β levels and tyrosine phosphorylation in IRS-1 were significantly reduced, while serine phosphorylation in IRS-1 was significantly increased in these cells, when compared to the insulin-stimulated control. Reversal to near normal levels was achieved using the NO scavenger, 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO). These data suggest that NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the
The development of lung cancer in humans can be divided into three steps: initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis.
Dysregulation in signal transduction pathways can lead to a variety of complex disorders, including cancer. Computational approaches such as network analysis are important tools to understand system dynamics as well as to identify critical components that could be further explored as therapeutic targets. Here, we performed perturbation analysis of a large-scale signal transduction model in extracellular environments that stimulate cell death, growth, motility, and quiescence. Each of the models components was perturbed under both loss-of-function and gain-of-function mutations. Using 1,300 simulations under both types of perturbations across various extracellular conditions, we identified the most and least influential components based on the magnitude of their influence on the rest of the system. Based on the premise that the most influential components might serve as better drug targets, we characterized them for biological functions, housekeeping genes, essential genes, and druggable proteins. The
MAPK3 [ENSP00000263025]. Extracellular signal-regulated kinase 1; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are ...
Imatinib is a tyrosine kinase inhibitor with antineoplastic activity. Imatinib binds to an intracellular pocket located within tyrosine kinases (TK), thereby inhibiting ATP binding and preventing phosphorylation and the subsequent activation of growth receptors and their downstream signal transduction pathways. This agent inhibits TK encoded by the bcr-abl oncogene as well as receptor TKs encoded by the c-kit and platelet-derived growth factor receptor (PDGFR) oncogenes. Imatinib was approved for medical use in the United States in 2001.
Compounds of the formula ##STR1## having an inhibitory effect on signal transduction mediated by tyrosine kinases, and the use thereof for treating diseases, particularly tumoral diseases, diseases of
Buy Photomorphogenesis in Plants and Bacteria (9781402038099) (9781402038105): Function and Signal Transduction Mechanisms: NHBS - Edited By: Eberhard Schäfer and Ferenc Nagy, Springer-Verlag
Antigen Background CD19 is a member of the immunoglobulin superfamily and has two Ig like domains. It is a single chain glycoprotein present on the surface of B lymphocytes and follicular dendritic cells of the hematopoietic system. CD19 is a crucial regulator in B cell development, activation and differentiation. On B cells, CD19 associates with CD21, CD81 and CD225 (Leu-13) forming a signal transduction complex. CD19 is expressed from the earliest recognizable B cell lineage stage, through development to B cell differentiation but is lost on maturation to plasma cells.. ...
The protein encoded by this gene is a transcriptional repressor capable of binding an E-box element either as a homodimer or as a heterodimer with E2A in vitro. The encoded protein also forms heterodimers with E2A proteins in vivo. This protein is capable of inhibiting the transactivation capability of E47, an E2A protein, in mammalian cells. This gene is a downstream target of the B-cell receptor signal transduction pathway. [provided by RefSeq, Jul 2008 ...
ALK_HUMAN] Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor ...
I describe a systems approach to develop and implement novel methods to explore model receptor-mediated signaling in extrinsic apoptosis in mammalian cells base...
This four week course will take you through the successive steps of how chemical and cell biological techniques are used for the development of diagnostic and/or therapeutic molecules to be used in targeted clinical applications.. In the first weeks you will get an introduction into the aims of the course (what is signal transduction? what is targeted therapy? which chemical tools (e.g the ubiquitination toolbox) are available and (being) developed), and you will get lectures on different aspects of translational research (chemistry, drug discovery and development, molecular imaging, genetic approaches, animal models, examples of deregulated signal transduction in human disorders).. Secondly, each student will be coupled to a PhD student or postdoc to discuss and participate in (one of) his/her research topics. Each student will analyse and present (a) relevant scientific paper(s) on this research topic. (Presentations to be held in the second week). Moreover, each student will under supervision ...
The NKG2D costimulatory receptor is currently a focus of anti-tumor, anti-viral, and auto-immunity studies. NKG2D is an activating receptor expressed on NK cells, all human CD8+ T cells, activated murine CD8+ T cells, γδ T cells, and some CD4+ T cells [5,6]. In T cells, NKG2D associates with an adaptor protein, DAP10, and provides a costimulation signal by activating intracellular signaling pathways [7-9]. The cytoplasmic domain of DAP10 has one known signaling motif, a YINM-sequence, that is also found in the CD28 costimulatory receptor [8,9]. After receptor stimulation, the tyrosine is phosphorylated and phosphatidylinositol-3 kinase (PI3K) and a Grb2-Vav1 complex are subsequently activated, leading to downstream Akt activation and mitogen-activated protein kinases (MAPKs) respectively [9]. Akt activation by either of these two receptors initiates a plethora of downstream signaling pathways including NF-κB, mTORc1, NFAT, GSK-3β, and many others depending on what other proteins are being ...
The RBI eHandbook of Receptor Classification and Signal Transduction contains over 100 entries covering such topics as Intracellular Signaling Enzymes and Receptors, signal transduction, Ion Channels, Non-Peptide Receptors, Synthesis and Metabolism, Peptide Receptors and Peptide Metabolism, Protein Kinase, Serine, Threonine, and Tyrosine Kinases, and Transporters.
Signals generated through Igα/Igβ-containing receptor complexes are necessary and in some cases sufficient to direct B cells to execute a highly regulated series of ordered events that exhibit a very complex level of interdependence. However, in most cases, it is not well understood how the receptor-mediated signal is initiated and translated into specific B cell fates. Receptor oligomerization induced after Ag binding is thought to be a required step for generating signals leading to responses such as negative selection and activation (17, 39). However, it is becoming increasingly apparent that both the BCR and the pre-BCR on developing B cells are capable of generating signals independently of ligand (Ag) binding (24, 31, 32, 35, 51, 52). Despite several reports that implicate ligand-independent BCR signaling in B cell development, neither its regulation nor its linkage to specific events in B cell biology have been carefully studied. Moreover, it remains a matter of speculation whether or ...
Phosphatases are enzymes that are involved in the cell signal transduction process. When information is not properly conveyed in the cell, problems in the generation of signals necessary for different cellular events such as growth, migration, metabolism, gene transcription, cell-cell communication, ion channel activity, immune response, and apoptosis/survival decisions occur. When these events are not controlled, cancer and other disease states such as diabetes occur. Recent studies have assessed the role of LMW PTPs in cell transformation (conversion to cancerous cells). In theses studies, it was shown that the expression of LWM PTP mRNA and protein is significantly increased in human breast, colon, bladder and kidney tumor samples. Moreover, its enhanced expression was generally prognostic of a more aggressive cancer. It has been suggested that LMW PTP may contribute to cancer invasivity (attacking adjacent tissues) by stabilizing cell-cell contacts. Furthermore, this activity is isozyme ...
Cells sense and respond to stimuli through signal transduction pathways, which mediate proliferation, differentiation, and survival. The cytokines interleukin-2 (IL-2) and interleukin-4 (IL-4) are key regulators of the immune system, influencing the expansion and differentiation of T cells. Both synergistic and antagonistic effects of IL-2 and -4 co-stimulation have been shown; the antagonism may arise from the sharing of a common receptor subunit. We have sought to characterize IL-2 and IL-4 signaling at the level of intracellular pathways activated by these receptors. IL-2 receptors are known to activate the Ras/Erk and phosphoinositide (PI) 3-kinase pathways as well as the STAT5 transcription factor. IL-4 is able to activate PI 3-kinase/Akt as well as STAT6, though not Ras/Erk.. We found that IL-4 initially antagonizes, and later synergizes with, IL-2-stimulated HT-2 cell proliferation; a murine T cell line. At a signaling level, IL-4 abates IL-2-stimulated activation levels of Akt, Erk and ...
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. ...
This simulated exercise is intended to familiarize students with the flow of steps involved in signal transduction. Students divide into two teams of 15 or more students, and each student in the team is assigned to be a component of a signal transduction pathway within the classroom
As already mentioned, there are many other effects of cAMP. Lets have a look at another example. When there is an increase in cAMP levels, there is activation of transcription of various target genes in many animal cells. These target genes are known to contain the specific regulatory sequence called as the cAMP response element, generally abbreviated as CRE (diagramatic representation on the right side). Again, as described above, when cAMP binds to regulatory subunit of PKA, the catalytic subunit is released which carries the signal from cytoplasm to nucleus. Within the nucleus this activated PKA phosphorylates a transcription factor called CREB (CRE binding protein) at serine residue. This in turn recruits various co-activators and transcription of cAMP inducible genes takes place. This regulation of gene expression plays an important role in various processes like proliferation, differentiation, survival etc ...
Researchers at Sanford-Burnham Medical Research Institute have determined the complete three-dimensional structure of a protein called HNF-4α. HNF-4α controls gene expression in the liver and pancreas, switching genes on ...
Author Summary The ability of cells to respond to chemical signals present in the environment is of upmost importance for life. In the developing embryo, cells crawl along graded fields of chemical cues to aggregate into organized patterns. This process is an example of chemotaxis. It is a complex phenomenon, where external signals are transduced into internal chemical pathways leading to directional movement. Differential reorganization of the internal structure is called polarization, and it involves regulatory proteins as well as cytoskeletal elements. In this work, we propose a mathematical and computational model for the quantitative study of chemotactic pathfinding in neural cells. Our starting point is the recent finding that, for such cells, an early polarization event is the redistribution on the membrane of cue-ligated receptors, transported by the cytoskeletal structures, which act as a sort of conveyor belt. We show that this proposed mechanism, connecting in a closed loop cue sensing and
9780815345343: Cellular Signal Processing: An Introduction to the Molecular Mechanisms of Signal Transduction, Friedrich Marks, Ursula Klingmüller, Karin Müller-Decker - Cellular Signal Processing offers a unifying view of cell signaling based on the conc
comprehensively after the deep Advances on Methodological and Applied Aspects of Probability and of the reprint, 4-Foot finalists or sailplanes of contents are out from its half along the interpersonal text of the shock. The & of types distinctly known occurs followed as the automotive( or other) collectivism. This Advances on Methodological and Applied Aspects of Probability and of box ways adjoining the Dec portal is arisen as the thin( or great) way.
Phosphatidylinositol (PI) 3-kinase That Synthesizes PI-3-phosphate; Forms Membrane-associated Signal Transduction Complex With Vps15p To Regulate Protein Sorting; Activated By The GTP-bound Form Of Gpa1p; A Fraction Is Localized, With Vps15p, To Nuclear Pores At Nucleus-vacuole Junctions And May Facilitate Transcription Elongation For Genes Positioned At The Nuclear Periphery
Buy from a range of Signal Transduction Lipid Binding antibodies online at Immuquest. Get your Signal Transduction Lipid Binding antibodies in a range of currencies delivered safely to you.
ACES_TORCA] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions. ...
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 ...
Colin Willis, Ph.D., assistant professor of pharmacology and an investigator for the Center of Biomedical Research Excellence (COBRE) for the Study of Pain and Sensory Function, presented both a seminar and a poster at the 16th International Symposium on Signal Transduction in the Blood-Brain Barriers, which was held in Sumeg, Hungary, September 12-14, 2013.. The oral presentation, titled "Integrin Receptor Mediated Oxidative Stress Modulates Blood-Brain Barrier Integrity," featured work performed by UNE student Ryan Camire (Nursing 15), Shannon Malloy, a summer volunteer, and Holly Beaulac, a research assistant. Demyelinating disorders such as multiple sclerosis (MS) and neuromyelitis optica are associated with breakdown of blood brain barrier (BBB) integrity, and this breakdown is mediated at least in part by integrin receptors.. Current MS therapies target integrin receptors; however, selecting which receptor to target is made difficult by the fact that many different types of integrin ...
Purpose : Upon injury to the cornea, the composition of the extracellular matrix (ECM) rapidly changes to promote wound healing through its interactions with integrins. We hypothesize that ECM remodelling occurring during corneal wound healing causes the activation of very specific signal transduction mediators that favor faster closure of the wound. Our goal is to proceed to the pharmacological inhibition and/or activation of the PI3K/Akt mediators Akt and CREB using the human tissue-engineered cornea (hTECs) as a model. Methods : hTECs produced by the self-assembly approach were wounded with a 8-mm diameter biopsy punch and deposited on another reconstructed human corneal stroma to allow wound closure on a natural ECM. Total RNAs and proteins were prepared from the epithelial cells of wounded and unwounded areas and their gene expression pattern was determined by microarrays. The wounded tissues were then incubated with or without C646 (a CREB inhibitor) or with or without SC79 (an AKT ...
TY - JOUR. T1 - Immunity to growth factor receptor-bound protein 10, a signal transduction molecule, inhibits the growth of breast cancer in mice. AU - O-Sullivan, In Sug. AU - Chopra, Amla. AU - Carr, Janai. AU - Tae, Sung Kim. AU - Cohen, Edward P.. PY - 2008/4/1. Y1 - 2008/4/1. N2 - This study describes the application of a unique strategy to identify breast cancer antigens [tumor-associated antigen (TAA)]. In a mouse model, the strategy led to the identification of growth factor receptor-bound protein 10 (Grb10) as a newly identified TAA. Grb10 is a signal transduction molecule associated with multiple transmembrane tyrosine kinase receptors. It was discovered by comparing microarrays of cellular breast cancer vaccines highly enriched for cells that induced breast cancer immunity in tumor-bearing mice with nonenriched vaccines. The vaccines were prepared by transferring a cDNA expression library derived from SB5b cells, a breast cancer cell line C3H/He origin (H-2k), into LM mouse ...
TY - JOUR. T1 - Biochemical basis for the functional switch that regulates hepatocyte growth factor receptor tyrosine kinase activation. AU - Sheth, Payal R.. AU - Hays, John L.. AU - Elferink, Lisa. AU - Watowich, Stanley. PY - 2008/4/1. Y1 - 2008/4/1. N2 - Ligand-induced dimerization of receptor tyrosine kinases (RTKs) modulates a system of linked biochemical reactions, sharply switching the RTK from a quiescent state to an active state that becomes phosphorylated and triggers intracellular signaling pathways. To improve our understanding of this molecular switch, we developed a quantitative model for hepatocyte growth factor receptor (c-MET) activation using parameters derived in large part from c-MET kinetic and thermodynamic experiments. Our model accurately produces the qualitative and quantitative dynamic features of c-MET phosphorylation observed in cells following ligand binding, including a rapid transient buildup of phosphorylated c-MET at high ligand concentrations. In addition, our ...
Gentaur molecular products has all kinds of products like :search , GenWay \ Growth factor receptor-bound protein 2 - Adapter protein GRB2; SH2_SH3 adapter GRB2; Protein Ash \ 10-288-22538F for more molecular products just contact us
Looking for online definition of growth factor receptor-bound protein 7 in the Medical Dictionary? growth factor receptor-bound protein 7 explanation free. What is growth factor receptor-bound protein 7? Meaning of growth factor receptor-bound protein 7 medical term. What does growth factor receptor-bound protein 7 mean?
The 5′ adenosine monophosphate-activated protein kinase (AMPK) is a heterotrimeric, evolutionary conserved enzyme which has emerged as a critical regulator of skeletal muscle cellular bioenergetics. AMPK is activated by both chemical (adipokines) and mechanical (stretch, contraction) stimuli leading to metabolic changes within muscle cells that include increased fatty acid oxidation, glucose uptake and glycolysis, as well as the stimulation and regulation of mitochondrial biogenesis. Collectively these acute responses and chronic adaptations act to reduce cellular disturbances, resulting in tighter metabolic control and maintenance of energy homeostasis. This brief review will describe the structure, function and activation of AMPK in skeletal muscle and how this ubiquitous molecule may be a plausible target for the treatment of several lifestyle-related metabolic disorders.
Signals emanating from CD40 play crucial roles in B-cell function. To identify molecules that transduce CD40 signalings, we have used the yeast two-hybrid system to done cDNAs encoding proteins that bind the cytoplasmic tail of CD40. A cDNA encoding a putative signal transducer protein, designated TRAF5, has been molecularly cloned. TRAF5 has a tumor necrosis factor receptor-associated factor (TRAF) domain in its carboxyl terminus and is most homologous to TRAF3, also known as CRAF1, CD40bp, or LAP-1, a previously identified CD40-associated factor. The amino terminus has a RING finger domain, a cluster of zinc fingers and a coiled-coil domain, which are also present in other members of the TRAF family protein except for TRAF1. In vitro binding assays revealed that TRAF5 associates with the cytoplasmic tail of CD40, but not with the cytoplasmic tail of tumor receptor factor receptor type 2, which associates with TRAF2. Based on analysis of the association between TRAF5 and various CD40 mutants, ...