Focus issue: fine-tuning Hedgehog signaling in development and disease.

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：:Overuse of β2-adrenoceptor agonist bronchodilators evokes receptor desensitization, decreased efficacy, and an increased risk of death in asthma patients. Bronchodilators that do not target β2-adrenoceptors represent a critical unmet need for asthma management. Here, we characterize the utility of osthole, a coumarin ...

journal_title：Science signaling

authors： Wang S,Xie Y,Huo YW,Li Y,Abel PW,Jiang H,Zou X,Jiao HZ,Kuang X,Wolff DW,Huang YG,Casale TB,Panettieri RA Jr,Wei T,Cao Z,Tu Y

更新日期：2020-11-24 00:00:00

abstract：:Store-operated Ca2+ entry (SOCE) is critical for salivary gland fluid secretion. We report that radiation treatment caused persistent salivary gland dysfunction by activating a TRPM2-dependent mitochondrial pathway, leading to caspase-3-mediated cleavage of stromal interaction molecule 1 (STIM1) and loss of SOCE. Afte...

journal_title：Science signaling

authors： Liu X,Gong B,de Souza LB,Ong HL,Subedi KP,Cheng KT,Swaim W,Zheng C,Mori Y,Ambudkar IS

更新日期：2017-06-06 00:00:00

abstract：:Chimeric antigen receptors (CARs) link an antigen recognition domain to intracellular signaling domains to redirect T cell specificity and function. T cells expressing CARs with CD28/CD3ζ or 4-1BB/CD3ζ signaling domains are effective at treating refractory B cell malignancies but exhibit differences in effector functi...

journal_title：Science signaling

authors： Salter AI,Ivey RG,Kennedy JJ,Voillet V,Rajan A,Alderman EJ,Voytovich UJ,Lin C,Sommermeyer D,Liu L,Whiteaker JR,Gottardo R,Paulovich AG,Riddell SR

更新日期：2018-08-21 00:00:00

abstract：:The mechanisms of context-specific differences in signal transduction, such as those that occur among different cell types, are not fully understood. One possibility is that differences in the abundance of proteins change signaling outputs because these proteins compete for binding to hub proteins at critical network ...

journal_title：Science signaling

authors： Kiel C,Verschueren E,Yang JS,Serrano L

更新日期：2013-12-17 00:00:00

abstract：:Chemoattractants induce cell migration through the activation of a distinct family of structurally related heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors. Over the past few years, several receptors in this family have been identified that recognize different classes of chemoattractants...

journal_title：Science signaling

authors： Borroni EM,Bonecchi R,Mantovani A,Locati M

更新日期：2009-02-24 00:00:00

abstract：:The CXC chemokine CXCL12 mediates the chemoattraction of T cells and enhances the stimulation of T cells through the T cell receptor (TCR). The adaptor SLP-76 [Src homology 2 (SH2) domain-containing leukocyte protein of 76 kD] has two key tyrosine residues, Tyr(113) and Tyr(128), that mediate signaling downstream of t...

journal_title：Science signaling

authors： Smith X,Schneider H,Köhler K,Liu H,Lu Y,Rudd CE

更新日期：2013-07-30 00:00:00

abstract：:Cytosolic pattern recognition receptors (PRRs) sense intracellular nucleic acids from pathogens such as bacteria and viruses, which leads to the induction of type I interferon (IFN) responses that are essential for an effective immune response. Further, these PRR pathways can be aberrantly activated by self DNA, which...

journal_title：Science signaling

authors： Bowie A

更新日期：2012-03-06 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：:Extracellular hyperosmolarity, or osmotic stress, generally caused by differences in salt and macromolecule concentrations across the plasma membrane, occurs in lymphoid organs and at inflammatory sites. The response of immune cells to osmotic stress is regulated by nuclear factor of activated T cells 5 (NFAT5), a tra...

journal_title：Science signaling

authors： Kino T,Takatori H,Manoli I,Wang Y,Tiulpakov A,Blackman MR,Su YA,Chrousos GP,DeCherney AH,Segars JH

更新日期：2009-02-10 00:00:00

abstract：:Neutrophil extracellular trap (NET) formation can generate short-term, functional anucleate cytoplasts and trigger loss of cell viability. We demonstrated that the necroptotic cell death effector mixed lineage kinase domain-like (MLKL) translocated from the cytoplasm to the plasma membrane and stimulated downstream NA...

journal_title：Science signaling

authors： D'Cruz AA,Speir M,Bliss-Moreau M,Dietrich S,Wang S,Chen AA,Gavillet M,Al-Obeidi A,Lawlor KE,Vince JE,Kelliher MA,Hakem R,Pasparakis M,Williams DA,Ericsson M,Croker BA

更新日期：2018-09-04 00:00:00

abstract：:The mechanisms that determine localized formation of reactive oxygen species (ROS) through NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase (Nox) family members in nonphagocytic cells are unknown. We show that the c-Src substrate proteins Tks4 (tyrosine kinase substrate with four SH3 domains...

journal_title：Science signaling

authors： Gianni D,Diaz B,Taulet N,Fowler B,Courtneidge SA,Bokoch GM

更新日期：2009-09-15 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：:Skeletal muscle mass is regulated by activity, metabolism, and the availability of nutrients. During muscle atrophy, MNK2 expression increases. We found that MNK2 (mitogen-activated protein kinase-interacting kinase 2), but not MNK1, inhibited proteins involved in promoting protein synthesis, including eukaryotic tran...

journal_title：Science signaling

authors： Hu SI,Katz M,Chin S,Qi X,Cruz J,Ibebunjo C,Zhao S,Chen A,Glass DJ

更新日期：2012-02-14 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：: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：:TRPM2 is a Ca2+-permeable cation channel that is specifically activated by adenosine diphosphoribose (ADPR). Channel activation in the plasma membrane leads to Ca2+ influx and has been linked to apoptotic mechanisms. The primary agonist, ADPR, is produced both extra- and intracellularly and causes increases in intrace...

journal_title：Science signaling

authors： Lange I,Yamamoto S,Partida-Sanchez S,Mori Y,Fleig A,Penner R

更新日期：2009-05-19 00:00:00

abstract：:Fgr is a member of the Src family of nonreceptor tyrosine kinases, which are overexpressed and constitutively active in many human cancers. Fgr expression is restricted to myeloid hematopoietic cells and is markedly increased in a subset of bone marrow samples from patients with acute myeloid leukemia (AML). Here, we ...

journal_title：Science signaling

authors： Shen K,Moroco JA,Patel RK,Shi H,Engen JR,Dorman HR,Smithgall TE

更新日期：2018-10-23 00:00:00

abstract：:Genetic diversity in human natural killer (NK) cell receptors is linked to resistance and susceptibility to many diseases. Here, we tested the effect of this diversity on the nanoscale organization of killer cell immunoglobulin-like receptors (KIRs). Using superresolution microscopy, we found that inhibitory KIRs enco...

journal_title：Science signaling

authors： Kennedy PR,Barthen C,Williamson DJ,Pitkeathly WTE,Hazime KS,Cumming J,Stacey KB,Hilton HG,Carrington M,Parham P,Davis DM

更新日期：2019-12-17 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：:The cytoplasmic phosphatase PTPN22 (protein tyrosine phosphatase nonreceptor type 22) plays a key role in regulating lymphocyte homeostasis, which ensures that the total number of lymphocytes in the periphery remains relatively constant. Mutations in PTPN22 confer an increased risk of developing autoimmune diseases; h...

journal_title：Science signaling

authors： Brownlie RJ,Miosge LA,Vassilakos D,Svensson LM,Cope A,Zamoyska R

更新日期：2012-11-27 00:00:00

abstract：:The V600E mutation in the kinase BRAF is frequently detected in melanomas and results in constitutive activation of BRAF, which then promotes cell proliferation by the mitogen-activated protein kinase signaling pathway. Although the BRAFV600E kinase inhibitor vemurafenib has remarkable antitumor activity in patients w...

journal_title：Science signaling

authors： Beck D,Niessner H,Smalley KS,Flaherty K,Paraiso KH,Busch C,Sinnberg T,Vasseur S,Iovanna JL,Drießen S,Stork B,Wesselborg S,Schaller M,Biedermann T,Bauer J,Lasithiotakis K,Weide B,Eberle J,Schittek B,Schadendorf D,G

更新日期：2013-01-29 00:00:00

abstract：:In Drosophila, recognition of microbe-specific molecules (such as bacterial peptidoglycans) activates serine protease cascades that converge to activate the Toll pathway. Recent data show that the serine protease Grass, which is activated downstream of pattern recognition receptors and was initially thought to be a co...

journal_title：Science signaling

authors： Ashok Y

更新日期：2009-01-06 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：:T helper (T(H)) cells integrate biochemical cues present in the tissue microenvironment and produce cytokines that orchestrate immune responses. Previous discoveries have revealed a qualitative understanding of how T(H) cells process this biochemical information; however, the lack of methods to quantify how well these...

journal_title：Science signaling

authors： Klinke DJ 2nd,Cheng N,Chambers E

更新日期：2012-04-17 00:00:00

abstract：:Toll-like receptor (TLR) signaling regulates macrophage activation and effector cytokine propagation in the constrained environment of a tissue. In macrophage populations, TLR4 stimulates the dose-dependent transcription of nuclear factor κB (NF-κB) target genes. However, using single-RNA counting, we found that indiv...

journal_title：Science signaling

authors： Bagnall J,Boddington C,England H,Brignall R,Downton P,Alsoufi Z,Boyd J,Rowe W,Bennett A,Walker C,Adamson A,Patel NMX,O'Cualain R,Schmidt L,Spiller DG,Jackson DA,Müller W,Muldoon M,White MRH,Paszek P

更新日期：2018-07-24 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

abstract：:Eps15 homology domain (EHD) proteins are conserved adenosine triphosphatases that are involved in membrane remodeling. EHD family members are structurally similar to the guanosine triphosphatase (GTPase) dynamin, and both are essential for the fission step of clathrin-mediated endocytosis. This Journal Club highlights...

journal_title：Science signaling

authors： Ioannou MS,Marat AL

更新日期：2012-04-24 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：: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