New connections: Manipulating NK cell responses.

abstract：:Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca2+ fluxes that are critical for many cellular fun...

journal_title：Science signaling

authors： Eckstein M,Vaeth M,Aulestia FJ,Costiniti V,Kassam SN,Bromage TG,Pedersen P,Issekutz T,Idaghdour Y,Moursi AM,Feske S,Lacruz RS

更新日期：2019-04-23 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：: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：:Hedgehog (Hh) signaling plays varied and critical roles in animal development, homeostasis, and disease. The core components of the canonical pathway and many key modulators of signaling have been identified, as have mechanisms by which the quantity and quality of signaling through the pathway are modulated. New resea...

journal_title：Science signaling

authors： VanHook AM

更新日期：2011-11-22 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：: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：: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：: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：:This two-issue series focuses on how understanding how signaling pathways are altered in cancer cells can enable researchers to develop more effective therapies. Cancer is a pleiotropic disease. Tumor cells change over time and, even within a specific tumor, cells may have different mutations and dependencies on diffe...

journal_title：Science signaling

authors： Gough NR

更新日期：2013-03-26 00:00:00

abstract：:The cytokines of the transforming growth factor-β (TGF-β) family promote the growth and differentiation of multiple tissues, but the role of only the founding member, TGF-β, in regulating the immune responses has been extensively studied. TGF-β is critical to prevent the spontaneous activation of self-reactive T cells...

journal_title：Science signaling

authors： Browning LM,Pietrzak M,Kuczma M,Simms CP,Kurczewska A,Refugia JM,Lowery DJ,Rempala G,Gutkin D,Ignatowicz L,Muranski P,Kraj P

更新日期：2018-08-28 00:00:00

abstract：:TLR4-stimulated B cell activation is mediated by the tyrosine kinase Syk and depends on the B cell receptor. ...

journal_title：Science signaling

authors： Foley JF

更新日期：2017-05-23 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：:New therapeutic approaches for chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis are needed because current treatments are often suboptimal in terms of both efficacy and the risks of serious adverse events. Inhibitor of apoptosis proteins (IAPs) are E3 ubiquitin liga...

journal_title：Science signaling

authors： Jensen S,Seidelin JB,LaCasse EC,Nielsen OH

更新日期：2020-02-18 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：:The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated t...

journal_title：Science signaling

authors： Lee JH,Mand MR,Kao CH,Zhou Y,Ryu SW,Richards AL,Coon JJ,Paull TT

更新日期：2018-01-09 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：: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 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：: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：: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：:The complexity of the signaling network that is initiated by members of the transforming growth factor-beta (TGF-beta) superfamily continues to increase. In addition, Smads, which were originally identified as key transducers of TGF-beta signals, are beginning to emerge as players in other TGF-beta-independent process...

journal_title：Science signaling

authors： Gough NR

更新日期：2008-11-18 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 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 proteasome plays a pivotal role in the cellular response to oxidative stress. Here, we used biochemical and mass spectrometric methods to investigate structural changes in the 26S proteasomes from yeast and mammalian cells exposed to hydrogen peroxide (H₂O₂). Oxidative stress induced the dissociation of the 20S co...

journal_title：Science signaling

authors： Wang X,Yen J,Kaiser P,Huang L

更新日期：2010-12-07 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：:Like phosphorylation, the addition of O-linked beta-N-acetylglucosamine (O-GlcNAcylation) is a ubiquitous, reversible process that modifies serine and threonine residues on nuclear and cytoplasmic proteins. Overexpression of the enzyme that adds O-GlcNAc to target proteins, O-GlcNAc transferase (OGT), perturbs cytokin...

journal_title：Science signaling

authors： Wang Z,Udeshi ND,Slawson C,Compton PD,Sakabe K,Cheung WD,Shabanowitz J,Hunt DF,Hart GW

更新日期：2010-01-12 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：:Notch signaling is used to choose cell fates in many developmental contexts. New evidence shows that circulating blood cells in Drosophila, in the absence of Notch ligand provided by neighboring cells, activate Notch signaling through stabilization with the hypoxia-inducible factor-α (HIF-α) transcription factor. Alth...

journal_title：Science signaling

authors： Johnson EA

更新日期：2011-07-12 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：:Compared with the luminal subtype, the basal-like subtype of breast cancer has an aggressive clinical behavior, but the reasons for this difference between the two subtypes are poorly understood. We identified microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) as basal-like subtype-specific miRNAs that decrease expr...

journal_title：Science signaling

authors： Stinson S,Lackner MR,Adai AT,Yu N,Kim HJ,O'Brien C,Spoerke J,Jhunjhunwala S,Boyd Z,Januario T,Newman RJ,Yue P,Bourgon R,Modrusan Z,Stern HM,Warming S,de Sauvage FJ,Amler L,Yeh RF,Dornan D

更新日期：2011-08-09 00:00:00