Using functional signature ontology (FUSION) to identify mechanisms of action for natural products.

abstract：:Oxygen sensing by the carotid body is essential in vertebrates to adapt to reduced arterial oxygen tension. In this issue of Science Signaling, Yuan et al. report an intricate signaling system to transduce a physical parameter--oxygen tension--into a biological cellular signal (neural discharge) through changes in the...

journal_title：Science signaling

authors： Fandrey J

更新日期：2015-04-21 00:00:00

abstract：:In this issue of Science Signaling, Lu et al reveal a role for Parkin-mediated mitophagy in beige-to-white adipocyte transition. In the absence of Parkin, mitochondria in thermogenic beige adipocytes are preserved even after the elimination of cold mimetic stimuli-in contrast to their typical elimination during the wh...

journal_title：Science signaling

authors： Sarraf SA,Youle RJ

更新日期：2018-04-24 00:00:00

abstract：:Inhibition of protein synthesis by phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2) at Ser(51) occurs as a result of the activation of a family of kinases in response to various forms of stress. Although some consequences of eIF2alpha phosphorylation are cytoprotective, phospho...

journal_title：Science signaling

authors： Mounir Z,Krishnamoorthy JL,Robertson GP,Scheuner D,Kaufman RJ,Georgescu MM,Koromilas AE

更新日期：2009-12-22 00:00:00

abstract：:TRPML1 (transient receptor potential mucolipin 1) is a Ca2+-permeable, nonselective cation channel localized to the membranes of endosomes and lysosomes and is not present or functional on the plasma membrane. Ca2+ released from endosomes and lysosomes into the cytosol through TRPML1 channels is vital for trafficking,...

journal_title：Science signaling

authors： Thakore P,Pritchard HAT,Griffin CS,Yamasaki E,Drumm BT,Lane C,Sanders KM,Feng Earley Y,Earley S

更新日期：2020-06-23 00:00:00

abstract：:The European Molecular Biology Organization (EMBO) meeting Visualizing Immune System Complexity, held in January 2009, covered multiple scales, from imaging single molecules to imaging whole animals. In addition to experimental details, there was an emphasis on modeling both for data analysis and as a predictive tool ...

journal_title：Science signaling

authors： Dustin ML

更新日期：2009-04-14 00:00:00

abstract：:Manipulating ligand interactions with the activating receptor NKG2D modulates natural killer cell responses. ...

journal_title：Science signaling

authors： Foley JF

更新日期：2017-05-30 00:00:00

abstract：:Ewing's sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is...

journal_title：Science signaling

authors： Zöllner SK,Selvanathan SP,Graham GT,Commins RMT,Hong SH,Moseley E,Parks S,Haladyna JN,Erkizan HV,Dirksen U,Hogarty MD,Üren A,Toretsky JA

更新日期：2017-10-03 00:00:00

abstract：:Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains un...

journal_title：Science signaling

authors： Levasseur EM,Yamada K,Piñeros AR,Wu W,Syed F,Orr KS,Anderson-Baucum E,Mastracci TL,Maier B,Mosley AL,Liu Y,Bernal-Mizrachi E,Alonso LC,Scott D,Garcia-Ocaña A,Tersey SA,Mirmira RG

更新日期：2019-12-03 00:00:00

abstract：:We previously developed a web tool, Transcriptomine, to explore expression profiling data sets involving small-molecule or genetic manipulations of nuclear receptor signaling pathways. We describe advances in biocuration, query interface design, and data visualization that enhance the discovery of uncharacterized biol...

journal_title：Science signaling

authors： Becnel LB,Ochsner SA,Darlington YF,McOwiti A,Kankanamge WH,Dehart M,Naumov A,McKenna NJ

更新日期：2017-04-25 00:00:00

abstract：:Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate the innate immune response through the production of cytokines. The innate immune response depends on the timing of encountering PAMPs, suggesting a short-term "memory." In particular, activation of TLR3 appears to prime ...

journal_title：Science signaling

authors： Liu B,Liu Q,Yang L,Palaniappan SK,Bahar I,Thiagarajan PS,Ding JL

更新日期：2016-07-12 00:00:00

abstract：:The hypoxia inducible factors (HIFs) and CCAAT/enhancer binding protein alpha (C/EBP alpha) are transcription factors that mediate adaptive responses to hypoxia and control aspects of energy metabolism, respectively. New evidence suggests that when HIF-1 alpha and C/EBP alpha interact, they bring about reciprocal func...

journal_title：Science signaling

authors： Janardhan HP

更新日期：2008-10-28 00:00:00

abstract：:Given its fundamental role in development and cancer, the Wnt-β-catenin signaling pathway is tightly controlled at multiple levels. RING finger protein 43 (RNF43) is an E3 ubiquitin ligase originally found in stem cells and proposed to inhibit Wnt signaling by interacting with the Wnt receptors of the Frizzled family....

journal_title：Science signaling

authors： Loregger A,Grandl M,Mejías-Luque R,Allgäuer M,Degenhart K,Haselmann V,Oikonomou C,Hatzis P,Janssen KP,Nitsche U,Gradl D,van den Broek O,Destree O,Ulm K,Neumaier M,Kalali B,Jung A,Varela I,Schmid RM,Rad R,Busch DH

更新日期：2015-09-08 00:00:00

abstract：:Understanding the complex dynamics of growth factor signaling requires both mechanistic and kinetic information. Although signaling dynamics have been studied for pathways downstream of receptor tyrosine kinases and G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors, they have not been inv...

journal_title：Science signaling

authors： Vizán P,Miller DS,Gori I,Das D,Schmierer B,Hill CS

更新日期：2013-12-10 00:00:00

abstract：:Obesity or a high-fat diet represses the endoribonuclease activity of inositol-requiring enzyme 1α (IRE1α), a transducer of the unfolded protein response (UPR) in cells under endoplasmic reticulum (ER) stress. An impaired UPR is associated with hepatic steatosis and nonalcoholic fatty liver disease (NAFLD), which is c...

journal_title：Science signaling

authors： Wang JM,Qiu Y,Yang Z,Kim H,Qian Q,Sun Q,Zhang C,Yin L,Fang D,Back SH,Kaufman RJ,Yang L,Zhang K

更新日期：2018-05-15 00:00:00

abstract：:The beta-amyloid (Abeta) peptide is associated with the pathogenesis of Alzheimer's disease (AD). Evidence gathered over the last two decades suggests that the gradual accumulation of soluble and insoluble Abeta peptide species triggers a cascade of events that leads to the clinical manifestation of AD. Abeta accumula...

journal_title：Science signaling

authors： Thathiah A,De Strooper B

更新日期：2009-10-20 00:00:00

abstract：:Insulin receptor substrate 2 (IRS2) is an adaptor protein that becomes tyrosine-phosphorylated in response to the cytokines interleukin-4 (IL-4) and IL-13, which results in activation of the phosphoinositide 3-kinase (PI3K)-Akt pathway. IL-4 and IL-13 contribute to allergic lung inflammation. To examine the role of IR...

journal_title：Science signaling

authors： Dasgupta P,Dorsey NJ,Li J,Qi X,Smith EP,Yamaji-Kegan K,Keegan AD

更新日期：2016-06-21 00:00:00

abstract：:Transforming growth factor-β (TGF-β) is a pluripotent cytokine that regulates cell fate and plasticity in normal tissues and tumors. The multifunctional cellular responses evoked by TGF-β are mediated by the canonical SMAD pathway and by noncanonical pathways, including mitogen-activated protein kinase (MAPK) pathways...

journal_title：Science signaling

authors： Hamidi A,Song J,Thakur N,Itoh S,Marcusson A,Bergh A,Heldin CH,Landström M

更新日期：2017-07-04 00:00:00

abstract：:During T cell activation by antigen-presenting cells (APCs), the diverse spatiotemporal organization of components of T cell signaling pathways modulates the efficiency of activation. Here, we found that loss of the tyrosine kinase interleukin-2 (IL-2)-inducible T cell kinase (Itk) in mice altered the spatiotemporal d...

journal_title：Science signaling

authors： Singleton KL,Gosh M,Dandekar RD,Au-Yeung BB,Ksionda O,Tybulewicz VL,Altman A,Fowell DJ,Wülfing C

更新日期：2011-10-04 00:00:00

abstract：:Jasmonates control defense gene expression, growth, and fertility throughout the plant kingdom and have been studied extensively in Arabidopsis thaliana. The prohormone jasmonic acid (JA) is conjugated to amino acids such as isoleucine to form the active hormone jasmonoyl-isoleucine (JA-Ile). A series of breakthroughs...

journal_title：Science signaling

authors： Gfeller A,Liechti R,Farmer EE

更新日期：2010-02-16 00:00:00

abstract：:Cellular dedifferentiation, the transition of differentiated somatic cells to pluripotent stem cells, ensures developmental plasticity and contributes to wound healing in plants. Wounding induces cells to form a mass of unorganized pluripotent cells called callus at the wound site. Explanted cells can also form callus...

journal_title：Science signaling

authors： Lee K,Park OS,Seo PJ

更新日期：2017-11-28 00:00:00

abstract：:Dimers of conventional transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) ligands are composed of two 100- to 140-amino acid peptides that are produced through the proteolytic processing of a proprotein precursor by proconvertases, such as furin. We report the identification of an evolutionarily...

journal_title：Science signaling

authors： Akiyama T,Marqués G,Wharton KA

更新日期：2012-04-03 00:00:00

abstract：:The activation of T cells requires the guanine nucleotide exchange factor VAV1. Using mice in which a tag for affinity purification was attached to endogenous VAV1 molecules, we analyzed by quantitative mass spectrometry the signaling complex that assembles around activated VAV1. Fifty VAV1-binding partners were ident...

journal_title：Science signaling

authors： Gaud G,Roncagalli R,Chaoui K,Bernard I,Familiades J,Colacios C,Kassem S,Monsarrat B,Burlet-Schiltz O,de Peredo AG,Malissen B,Saoudi A

更新日期：2018-07-10 00:00:00

abstract：:Prokaryotic cell wall biosynthesis is coordinated with cell growth and division, but the mechanisms regulating this dynamic process remain obscure. Here, we describe a phosphorylation-dependent regulatory complex that controls peptidoglycan (PG) biosynthesis in Mycobacterium tuberculosis. We found that PknB, a PG-resp...

journal_title：Science signaling

authors： Gee CL,Papavinasasundaram KG,Blair SR,Baer CE,Falick AM,King DS,Griffin JE,Venghatakrishnan H,Zukauskas A,Wei JR,Dhiman RK,Crick DC,Rubin EJ,Sassetti CM,Alber T

更新日期：2012-01-24 00:00:00

abstract：:Although many anticancer drugs that target receptor tyrosine kinases (RTKs) provide clinical benefit, their long-term use is limited by resistance that is often attributed to increased abundance or activation of another RTK that compensates for the inhibited receptor. To uncover common and unique features in the signa...

journal_title：Science signaling

authors： Wagner JP,Wolf-Yadlin A,Sevecka M,Grenier JK,Root DE,Lauffenburger DA,MacBeath G

更新日期：2013-07-16 00:00:00

abstract：:Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of s...

journal_title：Science signaling

authors： Ali H,Marth L,Krueger-Burg D

更新日期：2020-12-22 00:00:00

abstract：:The reciprocal regulation of phosphoprotein phosphatases (PPPs) by protein kinases is essential to cell cycle progression and control, particularly during mitosis for which the role of kinases has been extensively studied. PPPs perform much of the serine/threonine dephosphorylation in eukaryotic cells and achieve subs...

journal_title：Science signaling

authors： Nasa I,Cressey LE,Kruse T,Hertz EPT,Gui J,Graves LM,Nilsson J,Kettenbach AN

更新日期：2020-09-08 00:00:00

abstract：:The scattering of cultured epithelial cells in response to hepatocyte growth factor (HGF) is a model system that recapitulates key features of metastatic cell behavior in vitro, including disruption of cell-cell adhesions and induction of cell migration. We have developed image analysis tools that do not require fluor...

journal_title：Science signaling

authors： Loerke D,le Duc Q,Blonk I,Kerstens A,Spanjaard E,Machacek M,Danuser G,de Rooij J

更新日期：2012-07-03 00:00:00

abstract：:Stress is an important contributor to pathological conditions in humans. Hormonal changes that occur during acute and chronic stress situations can affect glucose homeostasis in both healthy people and in those with diabetes. Several studies have reported a negative effect of acute stress on maintenance of blood gluco...

journal_title：Science signaling

authors： Marcovecchio ML,Chiarelli F

更新日期：2012-10-23 00:00:00

abstract：:The aggregation of α-synuclein (αSyn) is considered a key pathophysiological feature of certain neurodegenerative disorders, collectively termed synucleinopathies. Given that a prion-like, cell-to-cell transfer of misfolded αSyn has been recognized in the spreading of αSyn pathology in synucleinopathies, we investigat...

journal_title：Science signaling

authors： Harischandra DS,Rokad D,Neal ML,Ghaisas S,Manne S,Sarkar S,Panicker N,Zenitsky G,Jin H,Lewis M,Huang X,Anantharam V,Kanthasamy A,Kanthasamy AG

更新日期：2019-03-12 00:00:00

abstract：:Endothelial cell dysfunction, characterized by a diminished response to endothelial cell-dependent vasodilators, is a hallmark of hypertension. TRPV4 channels play a major role in endothelial-dependent vasodilation, a function mediated by local Ca(2+) influx through clusters of functionally coupled TRPV4 channels rath...

journal_title：Science signaling

authors： Sonkusare SK,Dalsgaard T,Bonev AD,Hill-Eubanks DC,Kotlikoff MI,Scott JD,Santana LF,Nelson MT

更新日期：2014-07-08 00:00:00