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：: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：: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：:Cerebral amyloid angiopathy (CAA) is a vascular dysfunction disorder characterized by deposits of amyloid-β (Aβ) in the walls of cerebral vessels. CAA and Aβ deposition in the brain parenchyma contribute to dementia and Alzheimer's disease (AD). We investigated the contribution of platelets, which accumulate at vascul...

journal_title：Science signaling

authors： Donner L,Fälker K,Gremer L,Klinker S,Pagani G,Ljungberg LU,Lothmann K,Rizzi F,Schaller M,Gohlke H,Willbold D,Grenegard M,Elvers M

更新日期：2016-05-24 00:00:00

abstract：:The trimeric intracellular cation (TRIC) channels TRIC-A and TRIC-B localize predominantly to the endoplasmic reticulum (ER) and likely support Ca(2+) release from intracellular stores by mediating cationic flux to maintain electrical neutrality. Deletion and point mutations in TRIC-B occur in families with autosomal ...

journal_title：Science signaling

authors： Zhao C,Ichimura A,Qian N,Iida T,Yamazaki D,Noma N,Asagiri M,Yamamoto K,Komazaki S,Sato C,Aoyama F,Sawaguchi A,Kakizawa S,Nishi M,Takeshima H

更新日期：2016-05-17 00:00:00

abstract：:Alzheimer's disease (AD) is a progressive dementia disorder characterized by synaptic degeneration and amyloid-β (Aβ) accumulation in the brain. Through whole-genome sequencing of 1345 individuals from 410 families with late-onset AD (LOAD), we identified three highly penetrant variants in PRKCA, the gene that encodes...

journal_title：Science signaling

authors： Alfonso SI,Callender JA,Hooli B,Antal CE,Mullin K,Sherman MA,Lesné SE,Leitges M,Newton AC,Tanzi RE,Malinow R

更新日期：2016-05-10 00:00:00

abstract：:Group 3 innate lymphoid cells (ILC3s) are composed of subsets that are either positive or negative for the natural cytotoxicity receptor (NCR) NKp46 (encoded by Ncr1). ILC3s are located at mucosal sites, such as in the intestine and lung, where they are exposed to billions of commensal microbes and potentially harmful...

journal_title：Science signaling

authors： Viant C,Rankin LC,Girard-Madoux MJ,Seillet C,Shi W,Smyth MJ,Bartholin L,Walzer T,Huntington ND,Vivier E,Belz GT

更新日期：2016-05-03 00:00:00

abstract：:Both synaptic long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical for memory formation. Dell'Acqua and co-workers now demonstrate that transient postsynaptic incorporation of Ca(2+)-permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is required for...

journal_title：Science signaling

authors： Hell JW

更新日期：2016-04-26 00:00:00

abstract：:ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases Akt and ERK and induces cell death through the proapoptotic protein TRAIL. ONC201 is currently in early-phase clinical testing for various malignancies. We found through gene expression and prote...

journal_title：Science signaling

authors： Kline CL,Van den Heuvel AP,Allen JE,Prabhu VV,Dicker DT,El-Deiry WS

更新日期：2016-02-16 00:00:00

abstract：:The detection of microbes and initiation of an innate immune response occur through pattern recognition receptors (PRRs), which are critical for the production of inflammatory cytokines and activation of the cellular microbicidal machinery. In particular, the production of reactive oxygen species (ROS) by the NADPH ox...

journal_title：Science signaling

authors： Billings EA,Lee CS,Owen KA,D'Souza RS,Ravichandran KS,Casanova JE

更新日期：2016-02-02 00:00:00

abstract：:This year's signaling breakthroughs highlight insights into the pathogenesis or treatment of cancer, malaria, and neurodegenerative disorders; reveal molecular insights into cell death; and identify signals that could be leveraged to prevent plant parasitism or engineer bacteria as microbial fuel cells. ...

journal_title：Science signaling

authors： Adler EM

更新日期：2016-01-05 00:00:00

abstract：:Signaling pathways control cell fate decisions that ultimately determine the behavior of cancer cells. Therefore, the dynamics of pathway activity may contain prognostically relevant information different from that contained in the static nature of other types of biomarkers. To investigate this hypothesis, we characte...

journal_title：Science signaling

authors： Fey D,Halasz M,Dreidax D,Kennedy SP,Hastings JF,Rauch N,Munoz AG,Pilkington R,Fischer M,Westermann F,Kolch W,Kholodenko BN,Croucher DR

更新日期：2015-12-22 00:00:00

abstract：:Individual signaling pathways operate in the context of the broader signaling network. Thus, the response of a cell to signals from the environment is affected by the state of the signaling network, such as the clinically relevant example of whether some components in the network are inhibited. The cytokine tumor necr...

journal_title：Science signaling

authors： Gierut JJ,Wood LB,Lau KS,Lin YJ,Genetti C,Samatar AA,Lauffenburger DA,Haigis KM

更新日期：2015-12-15 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：:Interleukin-10 (IL-10) is an important anti-inflammatory cytokine that is produced primarily by macrophages. We investigated mechanisms by which the timing of IL-10 production was controlled in macrophages and found that cyclin-dependent kinase 5 (CDK5) activity was markedly increased in lipopolysaccharide (LPS)-stimu...

journal_title：Science signaling

authors： Na YR,Jung D,Gu GJ,Jang AR,Suh YH,Seok SH

更新日期：2015-11-24 00:00:00

abstract：:Cytotoxic lymphocytes share the presence of the activating receptor NK receptor group 2, member D (NKG2D) and the signaling-competent adaptor DNAX-activating protein 10 (DAP10), which together play an important role in antitumor immune surveillance. Ligand stimulation induces the internalization of NKG2D-DAP10 complex...

journal_title：Science signaling

authors： Quatrini L,Molfetta R,Zitti B,Peruzzi G,Fionda C,Capuano C,Galandrini R,Cippitelli M,Santoni A,Paolini R

更新日期：2015-10-27 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：:Double knockout of PTEN and LKB1-genes encoding phosphatase and tensin homolog and liver kinase B1, respectively-leads to the spontaneous development of cancer in mice. PTEN converts phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to phosphatidylinositol (4,5)-bisphosphate (PIP2), whereas LKB1 activates the 5' adeno...

journal_title：Science signaling

authors： Chen J,Zhang XD,Proud C

更新日期：2015-09-01 00:00:00

abstract：:The CLAVATA (CLV) and flagellin (flg) signaling pathways act through peptide ligands and closely related plasma membrane-localized receptor-like kinases (RLKs). The plant peptide CLV3 regulates stem cell homeostasis, whereas the bacterial flg22 peptide elicits defense responses. We applied multiparameter fluorescence ...

journal_title：Science signaling

authors： Somssich M,Ma Q,Weidtkamp-Peters S,Stahl Y,Felekyan S,Bleckmann A,Seidel CA,Simon R

更新日期：2015-08-04 00:00:00

abstract：:The endoplasmic reticulum (ER) has emerged as a critical regulator of cell survival. IRE1 is a transmembrane protein with kinase and RNase activities that is localized to the ER and that promotes resistance to ER stress. We showed a mechanism by which IRE1 conferred protection against ER stress-mediated cell death. IR...

journal_title：Science signaling

authors： Kanekura K,Ma X,Murphy JT,Zhu LJ,Diwan A,Urano F

更新日期：2015-06-23 00:00:00

abstract：:Cyclic-di-GMP (c-di-GMP) is a bacterial second messenger that transduces internal and external signals and regulates bacterial motility and biofilm formation. Some organisms encode more than 100 c-di-GMP-modulating enzymes, but only for a few has a signal been defined that modulates their activity. We developed and ap...

journal_title：Science signaling

authors： Mills E,Petersen E,Kulasekara BR,Miller SI

更新日期：2015-06-09 00:00:00

abstract：:Defects in the biogenesis of or transport through primary cilia affect Hedgehog protein signaling, and many Hedgehog pathway components traffic through or accumulate in cilia. The Hedgehog receptor Patched negatively regulates the activity and ciliary accumulation of Smoothened, a seven-transmembrane protein that is e...

journal_title：Science signaling

authors： Kim J,Hsia EY,Brigui A,Plessis A,Beachy PA,Zheng X

更新日期：2015-06-02 00:00:00

abstract：:The diacylglycerol kinases (DGKs) attenuate diacylglycerol (DAG)-mediated signals by catalyzing the conversion of DAG to phosphatidic acid. In T lymphocytes, the antigen-stimulated generation of DAG links signal strength to the intensity and duration of signaling by the Ras-extracellular signal-regulated kinase (ERK) ...

journal_title：Science signaling

authors： Mérida I,Andrada E,Gharbi SI,Ávila-Flores A

更新日期：2015-04-28 00:00:00

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：:The deubiquitylating enzyme OTUB1 is present in all tissues and targets many substrates, in both the cytosol and nucleus. We found that casein kinase 2 (CK2) phosphorylated OTUB1 at Ser(16) to promote its nuclear accumulation in cells. Pharmacological inhibition or genetic ablation of CK2 blocked the phosphorylation o...

journal_title：Science signaling

authors： Herhaus L,Perez-Oliva AB,Cozza G,Gourlay R,Weidlich S,Campbell DG,Pinna LA,Sapkota GP

更新日期：2015-04-14 00:00:00

abstract：:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous secreted peptide and, in preclinical studies, preferentially induces apoptosis in tumor cells rather than in normal cells. The acquisition of resistance in cells exposed to TRAIL or its mimics limits their clinical efficacy. Because kinas...

journal_title：Science signaling

authors： So J,Pasculescu A,Dai AY,Williton K,James A,Nguyen V,Creixell P,Schoof EM,Sinclair J,Barrios-Rodiles M,Gu J,Krizus A,Williams R,Olhovsky M,Dennis JW,Wrana JL,Linding R,Jorgensen C,Pawson T,Colwill K

更新日期：2015-04-07 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 transcription factor FOXP1 (forkhead box protein P1) is a master regulator of stem and progenitor cell biology. In diffuse large B cell lymphoma (DLBCL), copy number amplifications and chromosomal translocations result in overexpression of FOXP1. Increased abundance of FOXP1 in DLBCL is a predictor of poor prognos...

journal_title：Science signaling

authors： Walker MP,Stopford CM,Cederlund M,Fang F,Jahn C,Rabinowitz AD,Goldfarb D,Graham DM,Yan F,Deal AM,Fedoriw Y,Richards KL,Davis IJ,Weidinger G,Damania B,Major MB

更新日期：2015-02-03 00:00:00

abstract：:Type 1 diabetes mellitus (T1DM) is associated with chronic systemic inflammation and enhanced susceptibility to systemic bacterial infection (sepsis). We hypothesized that low insulin concentrations in T1DM trigger the enzyme 5-lipoxygenase (5-LO) to produce the lipid mediator leukotriene B4 (LTB4), which triggers sys...

journal_title：Science signaling

authors： Filgueiras LR,Brandt SL,Wang S,Wang Z,Morris DL,Evans-Molina C,Mirmira RG,Jancar S,Serezani CH

更新日期：2015-01-27 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：: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：:The prevailing view has been that N-terminally truncated p53 family isoforms (ΔNp53, ΔNp63, and DNp73) predominantly counteract cell cycle arrest and apoptosis. Recent progress in the field extend these well-known functions and place these isoforms in the center of a comprehensive regulatory network controlling major ...

journal_title：Science signaling

authors： Engelmann D,Pützer BM

更新日期：2014-09-30 00:00:00

abstract：:Pentraxin 3 (PTX3), a member of the long pentraxin subfamily within the family of pentraxins, is a soluble pattern recognition molecule that functions in the innate immune system. Innate immunity affords the infected host protection against sepsis, a potentially life-threatening inflammatory response to infection. Ext...

journal_title：Science signaling

authors： Daigo K,Nakakido M,Ohashi R,Fukuda R,Matsubara K,Minami T,Yamaguchi N,Inoue K,Jiang S,Naito M,Tsumoto K,Hamakubo T

更新日期：2014-09-16 00:00:00

abstract：:Under drought stress, abscisic acid (ABA) triggers closure of leaf cell pores called stomata, which are formed by two specialized cells called guard cells in plant epidermis. Two pathways downstream of ABA stimulate phosphorylation of the S-type anion channels SLAC1 (slow anion channel associated 1) and SLAH3 (SLAC1 h...

journal_title：Science signaling

authors： Maierhofer T,Diekmann M,Offenborn JN,Lind C,Bauer H,Hashimoto K,S Al-Rasheid KA,Luan S,Kudla J,Geiger D,Hedrich R

更新日期：2014-09-09 00:00:00

abstract：:In lymphocytes, the kinase Mst1 is required for the proper organization of integrins in the plasma membrane at the leading edge of migrating cells, which is critical for lymphocyte trafficking. We found a functional link between the small G protein Rab13 and Mst1 in lymphocyte adhesion and migration. In response to st...

journal_title：Science signaling

authors： Nishikimi A,Ishihara S,Ozawa M,Etoh K,Fukuda M,Kinashi T,Katagiri K

更新日期：2014-07-29 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

abstract：:Type I interferons (IFNs), including various IFN-α isoforms and IFN-β, are a family of homologous, multifunctional cytokines. IFNs activate different cellular responses by binding to a common receptor that consists of two subunits, IFNAR1 and IFNAR2. In addition to stimulating antiviral responses, they also inhibit ce...

journal_title：Science signaling

authors： Levin D,Schneider WM,Hoffmann HH,Yarden G,Busetto AG,Manor O,Sharma N,Rice CM,Schreiber G

更新日期：2014-05-27 00:00:00

abstract：:Antigen-mediated stimulation of the T cell receptor (TCR) triggers activation of nuclear factor κB (NF-κB), a key transcriptional regulator of T cell proliferation and effector cell differentiation. TCR signaling to NF-κB requires both the Carma1-Bcl10-Malt1 (CBM) complex and the inhibitor of κB (IκB) kinase (IKK) com...

journal_title：Science signaling

authors： Paul S,Traver MK,Kashyap AK,Washington MA,Latoche JR,Schaefer BC

更新日期：2014-05-13 00:00:00

abstract：:Plants and animals produce reactive oxygen species (ROS) in response to infection. In plants, ROS not only activate defense responses and promote cell death to limit the spread of pathogens but also restrict the amount of cell death in response to pathogen recognition. Plants also use hormones, such as salicylic acid,...

journal_title：Science signaling

authors： Siddique S,Matera C,Radakovic ZS,Hasan MS,Gutbrod P,Rozanska E,Sobczak M,Torres MA,Grundler FM

更新日期：2014-04-08 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