SMAC mimetics and RIPK inhibitors as therapeutics for chronic inflammatory diseases.

abstract：:Myeloproliferative neoplasms (MPNs) frequently have an activating mutation in the gene encoding Janus kinase 2 (JAK2). Thus, targeting the pathway mediated by JAK and its downstream substrate, signal transducer and activator of transcription (STAT), may yield clinical benefit for patients with MPNs containing the JAK2...

journal_title：Science signaling

authors： Winter PS,Sarosiek KA,Lin KH,Meggendorfer M,Schnittger S,Letai A,Wood KC

更新日期：2014-12-23 00:00:00

abstract：:A major endpoint of the canonical Wnt signaling pathway is a change in the transcription of target genes. The transcription factors lymphoid enhancer factor (LEF) and T cell factor (TCF) serve as the main gatekeepers of these changes by selecting genes to be targeted by the transcriptional coregulator beta-catenin and...

journal_title：Science signaling

authors： Hoverter NP,Waterman ML

更新日期：2008-09-30 00:00:00

abstract：:A system-wide analysis of cell signaling requires detecting and quantifying many different proteins and their posttranslational modification states in the same cellular sample. Here, we present Protocols for two miniaturized, array-based methods, one of which provides detailed information on a central signaling protei...

journal_title：Science signaling

authors： Luckert K,Gujral TS,Chan M,Sevecka M,Joos TO,Sorger PK,Macbeath G,Pötz O

更新日期：2012-01-10 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：:A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+) entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated activa...

journal_title：Science signaling

authors： Ong HL,de Souza LB,Zheng C,Cheng KT,Liu X,Goldsmith CM,Feske S,Ambudkar IS

更新日期：2015-01-13 00:00:00

abstract：:GIV (Gα-interacting vesicle-associated protein; also known as Girdin) enhances Akt activation downstream of multiple growth factor- and G protein (heterotrimeric guanosine 5'-triphosphate-binding protein)-coupled receptors to trigger cell migration and cancer invasion. We demonstrate that GIV is a tyrosine phosphoprot...

journal_title：Science signaling

authors： Lin C,Ear J,Pavlova Y,Mittal Y,Kufareva I,Ghassemian M,Abagyan R,Garcia-Marcos M,Ghosh P

更新日期：2011-09-27 00:00:00

abstract：:For decades, the fission yeast Schizosaccharomyces pombe has been used as an excellent model with which to explore how cellular growth is coordinated with the division cycle, a yet-unanswered question in biology. New studies in this organism show that TOR (target of rapamycin) kinase and stress-responsive MAPK (mitoge...

journal_title：Science signaling

authors： Shiozaki K

更新日期：2009-11-10 00:00:00

abstract：:Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca(2+) ...

journal_title：Science signaling

authors： Jian Z,Han H,Zhang T,Puglisi J,Izu LT,Shaw JA,Onofiok E,Erickson JR,Chen YJ,Horvath B,Shimkunas R,Xiao W,Li Y,Pan T,Chan J,Banyasz T,Tardiff JC,Chiamvimonvat N,Bers DM,Lam KS,Chen-Izu Y

更新日期：2014-03-18 00:00:00

abstract：:Activation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) by VEGF binding is critical for vascular morphogenesis. In addition, VEGF disrupts the endothelial barrier by triggering the phosphorylation and turnover of the junctional molecule VE-cadherin, a process mediated by the VEGFR2 downstream effec...

journal_title：Science signaling

authors： Gordon EJ,Fukuhara D,Weström S,Padhan N,Sjöström EO,van Meeteren L,He L,Orsenigo F,Dejana E,Bentley K,Spurkland A,Claesson-Welsh L

更新日期：2016-07-19 00:00:00

abstract：:Ligand binding to certain heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) stimulates the rapid synthesis of cyclic adenosine monophosphate (cAMP) through the G protein α(s) subunit, which activates adenylyl cyclase (AC). We found that the transmembrane receptor low-density lipop...

journal_title：Science signaling

authors： Wan M,Li J,Herbst K,Zhang J,Yu B,Wu X,Qiu T,Lei W,Lindvall C,Williams BO,Ma H,Zhang F,Cao X

更新日期：2011-03-15 00:00:00

abstract：:CD4(+)CD25(hi)Foxp3(+) regulatory T cells (T(regs)) are critical mediators of self-tolerance, which is crucial for the prevention of autoimmune disease, but T(regs) can also inhibit antitumor immunity. T(regs) inhibit the proliferation of CD4(+)CD25(-) conventional T cells (T(cons)), as well as the ability of these ce...

journal_title：Science signaling

authors： Schmidt A,Oberle N,Weiss EM,Vobis D,Frischbutter S,Baumgrass R,Falk CS,Haag M,Brügger B,Lin H,Mayr GW,Reichardt P,Gunzer M,Suri-Payer E,Krammer PH

更新日期：2011-12-20 00:00:00

abstract：:Signaling proteins evolved diverse interactions to provide specificity for distinct stimuli. Signaling complexity in the G protein (heterotrimeric guanosine triphosphate-binding protein) network was achieved in animals through subunit duplication and incremental evolution. By combining comprehensive and quantitative p...

journal_title：Science signaling

authors： Urano D,Maruta N,Trusov Y,Stoian R,Wu Q,Liang Y,Jaiswal DK,Thung L,Jackson D,Botella JR,Jones AM

更新日期：2016-09-20 00:00:00

abstract：:Vitamin E is a fat-soluble vitamin with antioxidant properties. Tocopherols are the predominant form of vitamin E found in the diet and in supplements and have garnered interest for their potential cancer therapeutic and preventive effects, such as the dephosphorylation of Akt, a serine/threonine kinase with a pivotal...

journal_title：Science signaling

authors： Huang PH,Chuang HC,Chou CC,Wang H,Lee SL,Yang HC,Chiu HC,Kapuriya N,Wang D,Kulp SK,Chen CS

更新日期：2013-03-19 00:00:00

abstract：:Educated natural killer (NK) cells have inhibitory receptors specific for self major histocompatibility complex (MHC) class I molecules and kill cancer cells more efficiently than do NK cells that do not have such receptors (hyporesponsive NK cells). The mechanism behind this functional empowerment through education h...

journal_title：Science signaling

authors： Staaf E,Hedde PN,Bagawath Singh S,Piguet J,Gratton E,Johansson S

更新日期：2018-02-13 00:00:00

abstract：:Slit proteins act as repulsive axon guidance cues by activating receptors of the Roundabout (Robo) family. During early neurogenesis in Drosophila melanogaster, Slit prevents the growth cones of longitudinal tract neurons from inappropriately crossing the midline, thus restricting these cells to trajectories parallel ...

journal_title：Science signaling

authors： Manavalan MA,Jayasinghe VR,Grewal R,Bhat KM

更新日期：2017-06-20 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：:Microglia mediate neuroprotection and neuropathogenesis but have not been directly associated with behavior. As gatekeepers of the brain's immune system, microglia protect the brain from pathogens but also contribute to inflammation, which may negatively affect neurons. A recent study demonstrates a role for Hoxb8-exp...

journal_title：Science signaling

authors： Antony JM

更新日期：2010-11-09 00:00:00

abstract：:Interleukin-2 (IL-2)-inducible T cell kinase (ITK) mediates T cell receptor (TCR) signaling primarily to stimulate the production of cytokines, such as IL-4, IL-5, and IL-13, from T helper 2 (TH2) cells. Compared to wild-type mice, ITK knockout mice are resistant to asthma and exhibit reduced lung inflammation and dec...

journal_title：Science signaling

authors： Sun Y,Peng I,Webster JD,Suto E,Lesch J,Wu X,Senger K,Francis G,Barrett K,Collier JL,Burch JD,Zhou M,Chen Y,Chan C,Eastham-Anderson J,Ngu H,Li O,Staton T,Havnar C,Jaochico A,Jackman J,Jeet S,Riol-Blanco L,Wu

更新日期：2015-12-01 00:00:00

abstract：:The cytokine interleukin-22 (IL-22), which is a member of the IL-10 family, is produced exclusively by immune cells and activates signal transducer and activator of transcription 3 (STAT3) in nonimmune cells, such as hepatocytes, keratinocytes, and colonic epithelial cells, to drive various processes central to tissue...

journal_title：Science signaling

authors： Lim C,Hong M,Savan R

更新日期：2016-09-27 00:00:00

abstract：:The interplay between calcium ion (Ca(2+)) and cyclic adenosine monophosphate (cAMP) signaling underlies crucial aspects of cell homeostasis. The membrane-bound Ca(2+)-regulated adenylyl cyclases (ACs) are pivotal points of this integration. These enzymes display high selectivity for Ca(2+) entry arising from the acti...

journal_title：Science signaling

authors： Willoughby D,Everett KL,Halls ML,Pacheco J,Skroblin P,Vaca L,Klussmann E,Cooper DM

更新日期：2012-04-10 00:00:00

abstract：:The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteo...

journal_title：Science signaling

authors： Gao J,Aksoy BA,Dogrusoz U,Dresdner G,Gross B,Sumer SO,Sun Y,Jacobsen A,Sinha R,Larsson E,Cerami E,Sander C,Schultz N

更新日期：2013-04-02 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：:MicroRNAs (miRNAs) are small noncoding RNAs that suppress the abundance of partially complementary mRNAs and inhibit their translation. Each miRNA can regulate hundreds of mRNAs, sometimes strongly but often weakly, to mediate a diverse array of biological functions, including proliferation, cell signaling, differenti...

journal_title：Science signaling

authors： Hata A,Lieberman J

更新日期：2015-03-17 00:00:00

abstract：:The accumulation of damaged or excess proteins and organelles is a defining feature of metabolic disease in nearly every tissue. Thus, a central challenge in maintaining metabolic homeostasis is the identification, sequestration, and degradation of these cellular components, including protein aggregates, mitochondria,...

journal_title：Science signaling

authors： Evans TD,Sergin I,Zhang X,Razani B

更新日期：2017-02-28 00:00:00

abstract：:The mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] inhibitor rapamycin is a potent inhibitor of T and B lymphocyte growth and proliferation. In this issue of Science Signaling, So et al found that the isoform of 4E-BP (4E-BP2) in lymphocytes that regulates messenger RNA translation is more sensitive...

journal_title：Science signaling

authors： Abraham RT

更新日期：2016-05-31 00:00:00

abstract：:Activation of Ca2+-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca2+ signals (Ca2+ sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries...

journal_title：Science signaling

authors： Khavandi K,Baylie RA,Sugden SA,Ahmed M,Csato V,Eaton P,Hill-Eubanks DC,Bonev AD,Nelson MT,Greenstein AS

更新日期：2016-10-11 00:00:00

abstract：:The oral bacterium Fusobacterium nucleatum is often found in colorectal cancer (CRC). In the 21 July 2020 issue of Science Signaling, Casasanta et al show that CRC cell-resident F. nucleatum promotes cytokine secretion that may potentiate tumor growth and metastatic progression in patients. ...

journal_title：Science signaling

authors： Meyerson M

更新日期：2020-08-11 00:00:00

abstract：:Secreted IgD concentration depends on the presence of microbiota. ...

journal_title：Science signaling

authors： Mushegian AA

更新日期：2017-02-21 00:00:00

abstract：:Premature labor and consequent neonatal mortality may be prevented by stimulating the expression of PIBF1 in uterine B cells. ...

journal_title：Science signaling

authors： Ferrarelli LK

更新日期：2017-01-17 00:00:00

abstract：:The role of the mitochondrial Ca2+ uniporter (MCU) in physiologic cell proliferation remains to be defined. Here, we demonstrated that the MCU was required to match mitochondrial function to metabolic demands during the cell cycle. During the G1-S transition (the cycle phase with the highest mitochondrial ATP output),...

journal_title：Science signaling

authors： Koval OM,Nguyen EK,Santhana V,Fidler TP,Sebag SC,Rasmussen TP,Mittauer DJ,Strack S,Goswami PC,Abel ED,Grumbach IM

更新日期：2019-04-30 00:00:00